In order to clarify the clinical response of long-term adjuvant chemotherapy using Carmofur (HCFU), a comparative multicenter trial has been performed by a randomized controlled method. Curative resected patients suffering from stomach cancer were randomly allocated into two arms. Arm A consisted of short-term MF chemotherapy (mitomycin C 0.04 mg/kg plus 5-fluorouracil 5.0 mg/kg x 6 bolus i.v.) and arm B consisted of arm A plus long-term HCFU chemotherapy (HCFU 6-12 mg/kg/day over 12 weeks, p.o.). The difference of overall survival probability between the two studied arms significantly supported arm B therapy (generalized Wilcoxon test: p = 0.0405) up to 5 years after surgery. The difference of the survival curves was clearer in the case of patients with cancers in the advanced stage, such as a positive serosal inversion and a lymph node metastases [ps(+).n(+)]. The side effects of HCFU, most patients experiencing subjective symptoms such as gastrointestinal toxicities, polyuria, and hot sensation, were reversible. Our results suggest that HCFU maintenance therapy has effect on preventing the postsurgical recurrences of stomach cancer and elongating the patient's survival.