Background: Neo-angiogenesis is particularly abundant in SCLC and associated with poor prognosis. Considering promising signals in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line chemotherapy with cisplatin-etoposide for treatment of extensive disease (ED) SCLC. Methods: Patients were randomized to receive either etoposide 100 mg/m² i.v. and cisplatin 25 mg/m²on days 1-3 (or carboplatin AUC 5 in day 1) (arm A) or same chemotherapy combined with bevacizumab 7.5 mg/kg i.v. on day 1 (arm B), every 3 weeks and for a maximum of 6 courses; in the absence of progression after 6 cycles patients in arm B continued bevacizumab alone until progression or for a maximum of 18 courses. The primary end-point was overall survival (OS). Results:From November 2009 to October 2015, a total of 204 patients were randomized in the two arms (103 in arm A vs. 101 in arm B); 198 patients were considered in intention-to-treat analysis (102 in arm A and 96 in arm B; 6 patients did not receive the assigned treatment). Patients characteristics were: 68% and 70% male, 89% and 93% PS 0-1 patients in arm A and B, respectively; median age was 64 years (range 41-81). Concerning the hematological toxicity, no statistically significant differences were observed between the two arms; concerning the non-hematological toxicity, only hypertension was more frequent in arm B (grade 3-4 1% vs. 6% of patients; p = 0.033); no grade 3-4 proteinuria or hemorrhage was registered. At a median follow-up of 35 months, median PFS was 5.7 vs. 6.7 months (HR: 0.72; 95%CI 0.54-0.97; p = 0.030), median OS was 8.9 vs. 9.8 months and 1-year survival rate was 25% vs. 37% (HR: 0.78; 95%CI 0.58-1.06; p = 0.113) in arm A and B, respectively. Conclusion: The addition of bevacizumab to platinum-etoposide in the first-line treatment of ED SCLC leads to a statistically significant improvement in PFS, with an acceptable toxicity profile. However only a not statistically significant increase in OS was observed. Further research in the area of angiogenesis therapy of SCLC is warranted. Clinical trial information: 2007-007949-13.