Background: There is still a debate regarding whether regimens combining irinotecan with platinum could replace regimens combining etoposide with platinum, as first-line chemotherapy for extensive-stage small cell lung cancer (ES-SCLC). We performed a meta-analysis to compare these regimens as first-line chemotherapy for ES-SCLC. Methods: A literature search for randomized controlled trials was performed using the Cochrane Library, PubMed, and Embase. The inverse variance method was used to estimate summary hazard ratios and their 95% confidence intervals for overall survival and progression free survival. Relative risk was used to estimate the overall response rate, disease control rate, 1-year survival, 2-year survival, and adverse event data. Result: Nine randomized controlled trials (2451 patients) were included. Regimens combining irinotecan and platinum improved overall survival, progression-free survival and overall response rate compared to combination etoposide and platinum regimens. Meanwhile, superior progression-free survival and overall response rate outcomes were observed in the Asian subgroup of patients. These patients receiving a combination irinotecan and platinum regimen experienced grade 3-4 diarrhea more frequently and experienced less hematologic toxic events than the non-Asian groups. Conclusions: Our data suggest that a combination irinotecan and platinum regimen can prolong overall survival, progression-free survival and overall response rate for patients with ES-SCLC as compared to a combination etoposide and platinum regimen. And the Asian patients could benefit from irinotecan combined with platinum easier.