Platinum-fluoropyrimidine combinations are the preferred first-line options for advanced gastric cancer (AGC) in East Asia. On the other hand, docetaxel-containing regimens without platinum have demonstrated promising activity in AGC. However, dose-related toxicity of docetaxel has limited its clinical adoption. This study compared the efficacy and safety of a modified low-dosed docetaxel plus S-1 (mDS) with oxaliplatin plus S-1 (SOX) in Chinese patients with AGC. Patients were assigned to receive either oxaliplatin (100 mg/m(2)) in the SOX arm or docetaxel (40 mg/m(2)) in the mDS arm on day 1 of every 3-week cycle. S-1 80-120 mg/day was administered orally on days 1-14 in the 3-week cycle in both groups. One hundred and eighty-eight patients (mDS regimen 101; SOX 87) showed similar overall survival (OS; 13.1 vs 12.8 months, P = 0.878), progression-free survival (PFS; 5.8 vs 5.5 months, P = 0.924), and overall response rate (39.7 vs 44.2%, P = 0.569) in the mDS and SOX arms, respectively. mDS was associated with significantly less grade 3/4 toxicities in thrombocytopenia (5.9 vs 16.1%) and gastrointestinal disturbances (1.0 vs 8.0%). Furthermore, in patients who had ever received oxaliplatin-based adjuvant chemotherapy (N = 40), mDS resulted in significantly superior OS (17.8 vs 9.5 months, P = 0.015) and PFS (7.0 vs 4.2 months, P = 0.008) compared with SOX. In conclusion, mDS was as effective as SOX in Chinese patients with AGC, but it resulted in a significantly improved tolerability. In patients who received oxaliplatin-based adjuvant chemotherapy before, mDS was associated with improved efficacy in the first-line setting.