OBJECTIVE: To examine the prevalence of anemia and its impact of hemoglobin (Hgb) levels in predicting outcomes of 5-fluorouracil (FU)-based first-line chemotherapy for patients with advanced gastric cancer (AGC). METHODS: We collected data retrospectively from 511 consecutive patients treated with FU-based first-line chemotherapy as a routine clinical practice for AGC and followed up in two centers from 1995 to 2003. FU was given in combination with cisplatin (61%), taxanes (12%), anthracyclines (24%) and/or folinic acid (50%). RESULTS: Hgb values were <10 g/dl in 41%, and patients with baseline Hgb levels <10 g/dl had significantly lower response rates (9%) than patients with Hgb > or = 10 g/dl (53%; P < 0.001). In addition, Hgb < 10 g/dl served as a predictor for disease progression (RR, 1.77; 95% CI, 1.42-2.21) and death (RR, 1.85; 95% CI, 1.48-2.32) along with chemotherapy response and performance status. CONCLUSION: Low baseline Hgb level is a strong and independent prognostic factor for the outcomes of AGC patients receiving FU-based first-line chemotherapy. This results strongly suggest that Hgb level, along with performance status, may be considered as a stratification variable in subsequent studies of AGC.