The best choice of chemotherapy regimen for patients with advanced gastric cancer (AGC) is still a matter of controversy and requires further investigation. This study was performed to evaluate the efficacy and safety of intra-arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and mitomycin C 10 mg/m (FCM) repeated every 6 weeks, as first-line treatment for AGC. Forty-seven (95.9%) of the 49 patients were assessable for response. Four cases of complete response and 28 cases of partial response were confirmed, giving an overall response rate of 65.3% [95% confidence interval (CI): 52.0-78.6%]. The median time to progression and overall survival for all patients was 8.3 months (95% CI: 6.8-9.8 months) and 14.5 months (95% CI: 12.0-17.0 months). The estimate of overall survival at 12 and 24 months was 55.1% (95% CI: 41.2-69.0%) and 18.4% (95% CI: 7.5-29.2%), respectively. Most patients experienced neutropenia during their course of therapy with 21.3% of patients (n = 10) for grade 3/4 neutropenia. Grade 3 stomatitis, lethargy, and palmar-plantar erythema were observed in two (4.3%), eight (17.0%), and one (2.1%) patients, respectively. Yet, no grade 4 nonhematological toxicity was observed. Intra-arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and mitomycin C 10 mg/m is a tolerated treatment modality with promising activity in patients with previously untreated AGC.