The majority of previous studies of lobaplatin in small cell lung cancer (SCLC) are small phase I-II studies. The present study aimed to verify the non-inferiority (in terms of efficacy) of lobaplatin plus etoposide (EL) vs. cisplatin plus etoposide (EP) in patients with previously untreated extensive-stage SCLC (ES-SCLC). This phase III non-inferiority randomized clinical trial enrolled patients at 17 sites between September 2010 and May 2013. Patients were randomized to EL (30 mg/m(2) lobaplatin on day 1 and 100 mg/m(2) etoposide on days 1-3, for 21-day cycles) or EP (80 mg/m(2) cisplatin on day 1 and 100 mg/m(2) etoposide on days 1-3, for 21-day cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR), toxicity and quality of life (QoL). A total of 234 patients were randomized to the EL (n=122) and EP (n=112) treatment groups. The median PFS, median OS and DCR were 5.1 vs. 5.3 months (P=0.786), 10.6 vs. 9.7 months (P=0.701) and 85.5 vs. 86.7% (P=0.848) in the EL vs. EP groups, respectively. Patients in the EL group had significantly lower frequencies of nephrotoxicity (2.5 vs. 11.7%; P=0.008), nausea (22.3 vs. 40.5%; P=0.003) and vomiting (14.1 vs. 35.1%; P<0.001) than those in the EP group. Overall, EL was not inferior to EP in terms of PFS and OS. The tolerance and QoL of the EL regimen were better than those of the EP regimen. EL is thus an alternative choice for the first-line treatment of ES-SCLC.