Background: Doublet chemotherapy with S-1 and cisplatin (CS) is one of the standard first-line chemotherapy for advanced gastric cancer in Japan. Triplet chemotherapy with docetaxel added to CS (DCS) showed a promising activity associated with feasible toxicities in a phase II study. We conducted a phase III study, JCOG1013, to investigate whether DCS improved overall survival (OS) compared with CS. Methods: Patients with previously untreated, human epidermal growth factor receptor 2 negative or unknown, unresectable or recurrent gastric adenocarcinoma, performance status 0 to 1, and adequate organ function were eligible. They were randomly 1:1 assigned to receive CS (S-1 40-60 mg orally twice a day for 3 weeks, cisplatin 60 mg/m² on day 8, repeated every 5 weeks), or DCS (docetaxel 40 mg/m², cisplatin 60 mg/m² on day 1, S-1 40-60 mg orally twice a day for 2 weeks, repeated every 4 weeks). The primary endpoint was OS. A total of 740 patients were required to detect an increase in median OS from 13.5 months in the CS arm to 16.5 months in the DCS arm, corresponding to a hazard ratio (HR) of 0.8435, with a one-sided alpha of 5% and power of 80%. Results: From Apr 2012 to Mar 2016, 741 patients were enrolled in total (CS 371, DCS 370). Median OS was 14.2 and 15.3 months for DCS and CS, respectively (HR 0.99; 95% confidence interval [CI] 0.85-1.16; one-sided stratified log-rank p = 0.47). By histological subtypes, median OS was 13.3 months for DCS and 14.2 months for CS (p = 0.83) in the diffuse type (n = 482), and 17.5 months for both DCS and CS (p = 0.65) in the intestinal type (n = 259). Median progression-free survival was 7.4 months for DCS and 6.5 months for CS (HR 0.99; 95% CI, 0.86-1.15; p = 0.92). The overall response rate was 59.3% for DCS and 56.0% for CS (p = 0.50). The most common adverse events of grade 3 or 4 were neutropenia (DCS 58.5%, CS 32.1%), febrile neutropenia (DCS 7.6%, CS 5.7%), and diarrhea (DCS 7.0%, CS 7.4%). Conclusions: Addition of docetaxel to CS failed to improve OS of patients with untreated advanced gastric cancer. Therefore, CS remains the standard treatment for first-line chemotherapy for advanced gastric cancer. Clinical trial information: UMIN000007652.