Background: Open splenectomy is a useful procedure for some diseases with splenomegaly > 1500 g. We undertook this study to evaluate morbidity and mortality of open splenectomy at the Instituto Nacional de Cancerologia in Mexico City. Methods: We reviewed the clinical files of patients with benign and malignant hematological diseases, as well as other diseases, who underwent splenectomy from 1994 to 2005. Results: Twenty five patients with a mean age of 38.5 years were submitted for open splenectomy. Splenomegaly was found in 12 patients (48%). The most frequent abdominal wall incision was transverse left subcostal (64%). Average surgical time was 125 min, bleeding 485 ml, spleen weight 1553.6 g and average size 15 x 11 x 12 cm. Average hospital stay was 7.5 days. Eighteen patients (72%) did not have immediate complications. One patient (4%) developed surgical wound infection, two patients (8%) had significant pain, three patients (12%) had bleeding and one patient (4%) developed intraabdominal fluid collection. Twenty one patients (84%) did not have further complications. One patient (4%) developed multiple organ failure, another patient (4%) developed thrombocytopenia and another (4%) developed severe pain. During an average 81-month follow-up we found 14 asymptomatic patients (56%), two patients (8%) with documented tumoral activity (angiosarcoma and non-Hodgkin's lymphoma) and one patient (4%) developed a second neoplasm. Six patients (24%) died due to underlying disease (chronic myeloid leukemia and lymphoma), one patient (4%) with active disease (Hodgkin's disease) and one patient (4%) died due to other causes. Conclusions: With a spleen > 1500 g, open surgery offers better visibility and lower morbidity and mortality.