Background and Aims: Novel motorized spiral enteroscopy (NMSE) is a recent advancement in the field of enteroscopy and offers multiple features, including self-propulsion, better irrigation, and shorter enteroscope length with a larger channel. The aim of this study was to evaluate the efficacy in terms of diagnostic yield and therapeutic success of NMSE in patients undergoing enteroscopy by antegrade and/or retrograde approaches for suspected small-bowel disease. Methods: We retrospectively evaluated consecutive patients with symptomatic small-bowel disease who underwent enteroscopy over a 6-month period. Diagnostic yield, therapeutic success, total enteroscopy rate (TER), technical success, total procedural time, depth of maximal insertion, and adverse events related to the NMSE procedure were noted. Results: Of 61 patients (mean age, 45.67 +/- 15.37 years; 43 men) included for NMSE, 57 patients underwent successful enteroscopy with a technical success of 93.4%. The overall diagnostic yield was 65.5% (95% confidence interval, 52.31-77.27) and 70.1% (95% confidence interval, 56.60-81.57) in patients who underwent successful NMSE; TER was 60.6%: 31.1% by the antegrade approach and 29.5% by a combined antegrade and retrograde approach. Depth of maximal insertion and procedural time was of 465 cm (range, 100-650) and 40 minutes (range, 25-60), respectively, by the antegrade approach and 140 cm (range, 50-200) and 35 minutes (range, 30-60) by the retrograde route. Lesions were classified as inflammatory (n = 25), vascular (n = 10), and mass (n = 4). Biopsy specimens were obtained in 50.8% subjects, and 23% patients underwent therapeutic procedures. No major adverse events were seen. Conclusions: NMSE is a promising technology, showing high efficacy as a diagnostic and therapeutic tool in the management of otherwise difficult-to-treat small-bowel disease.