Background: Asthma is a chronic inflammatory pulmonary disorder that is characterized by reversible obstruction of the airways. Allergic rhinitis and allergic asthma are chronic inflammatory conditions that frequently co-exist, both with hallmark eosinophils. Immunotherapy is an established treatment of allergic diseases. Non-injective routes for immunotherapy such as the sublingual route are thought to be valuable therapeutic options for respiratory allergy and have the primary aim of minimizing the risk of adverse events and of improving the compliance of the patients. Sublingual immunotherapy is now officially accepted as a viable alternative to the traditional subcutaneous route. Aim of the work: In the present study, a trial has been made to administer the sublingual immunotherapy using multiple allergens in allergic asthmatic Patients with and without allergic rhinitis and to evaluate the clinical efficacy, safety, and changes in allergen-specific antibodies during sublingual immunotherapy (SLIT). Patients and methods: This study was conducted at Kingdom of Saudi Arabia. The present study comprised two groups; group I included 20 asthmatic patients (13 males and 7 females) with a mean age of (29.05 +/- 8.27 years). Group II included 20 male asthmatic patients with allergic rhinitis with a mean age of (33.61 +/- 6.43 years). All patients were subjected to careful history taking and careful clinical examination, routine laboratory investigations, chest X ray PA, X ray paranasal sinuses, eosinophilic blood count and total IgE in serum by ELISA technique before start, after 6 months and after one year of the course of the sublingual immunotherapy, skin prick test and specific IgE to food and inhalants, Pulmonary function testing (spirometry) before start and after one year of the course of the sublingual immunotherapy. Results: Our results revealed that 8 out of 20 asthmatic patients group (40%) had nocturnal asthma and 11 patients (55%) had asthmatic attacks. On the other hand, 12 patients (60%) of asthmatic patients with allergic rhinitis had nocturnal asthma and asthmatic attacks. Our study revealed that, there were statistically significant decreases in blood eosinophils one year after SLIT compared to that before SLIT in both asthmatic patients with and without allergic rhinitis. Our study showed there were statistically insignificant decrease in total IgE in asthmatic patients group and statistically significant decrease in total IgE in asthmatic patients with allergic rhinitis one year after SLIT compared to that before SLIT. Results of specific IgE to food and inhalants revealed that, there were statistically significant reduction of number of allergens from 3.65 +/- 1.60 to 1.55 +/- 1.27 in asthmatic group and from 3.95 +/- 2.11 to 1.35 +/- 1.34) in asthmatics with allergic rhinitis group (P<0.05) one year after SLIT compared to that before SLIT. Results of skin prick test revealed that, there were statistically significant reduction of number of allergens from (3.30 +/- 1.30 to .55 +/- 1.19) in asthmatic group and from (4.1 +/- 2.1 to 1.1 +/- 1.33) in asthmatics with allergic rhinitis group (P<0.05) one year after SLIT compared to that before SLIT. The majority of asthmatic patients group were sensitive to mites (60%), followed by mixed grass pollens (30%), Penicillium notatum (25%), house dust (20%), Cockroach (20%) respectively. On the other hand, the majority of asthmatic patients with allergic rhinitis group were sensitive to mites (75%), house dust (40%), mixed grass pollens (40%), mixed pollens (30%), cat epithelium (30%), Penicillium notatum (25%), Cockroach (25%), dog epithelium (20%), and sheep wool (20%). Results of Pulmonary function in both asthmatic patients group and asthmatic patients with allergic rhinitis showed statistically significant increase in FVC, FEV1, PEF, FEF25%, FEF50% and MVV one year after SLIT compared to that before SLIT. As regard the duration of sublingual immunotherapy one patient (5%) of asthma group discontinued treatment after one year, two (10%) after 18 months, 3 (15%) after 2 years, and 14 (70%) continue >2 years. Two patients (10%) of asthma allergic rhinitis group discontinued treatment after one year, 2 (10%) after 18 months, 4 (20%) after 2 years, and 12 (60%) continue >2 years. Local reverse reactions (throat itching) were reported in one (5%) patient of asthma group. No other local side effects or systemic side effects were reported in both asthmatic patients and asthmatic with allergic rhinitis group. From the twenty asthmatic group, 11 patients (55%) tolerated sublingual immunotherapy therapy very well, 7 (35%) good, 2 (10%) moderate. On the other hand, 10 asthmatic patients with allergic rhinitis (50%) tolerated therapy very well, 6 patients (30%) good, and 4 patients (20%) moderate. Our results revealed that 13 out of 20 (65%) asthmatic patients group had reduction of symptoms, 7 out of 8 patients (87.5%) had reduction of nocturnal asthma, 7 out of 11 patients (63.63%) had reduction of asthmatic attacks and 14 out of 20 patients (70%) had reduction of need to rescue treatment one year after the course of sublingual immunotherapy. On the other hand, 15 out of 20 (75%) asthmatic patients with allergic rhinitis group had reduction of symptoms, 11 out of 12 patients (91.66%) had reduction of nocturnal asthma, 9 out of 12 patients (75%) had reduction of asthmatic attacks 15 out of 20 patients (75%) had reduction of need to rescue treatment, and 13 patients (65%) had reduction of nasal symptoms one year after the course of sublingual immunotherapy. Conclusion: From this study we concluded that sublingual immunotherapy is a safe treatment which significantly reduces symptoms and medication requirements, improves lung function in both asthmatic patients with and without allergic rhinitis. SLIT using multiple allergens lowered the allergen burden in both asthmatic patients with and without allergic rhinitis. [Emara M.M., Mansour H.A., Shehata M.T. and Zakia Abu-Zahab. Outcome of Sublingual Immunotherapy with Multiple Allergens in Asthmatic Patients with and without Allergic Rhinitis. Life Sci J 2012;9(3):817-829]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 116