Excision repair cross-complementation 1 (ERCC1) has been reported to play a major role in the response to platinum-based therapies. It has recently been proposed that a synonymous polymorphism at codon 118 converting a common codon usage (AAC) to an infrequent one (AAT) may impair ERCC1 translation and to affect the response to cisplatin chemotherapy. We analyzed the association between this polymorphism and clinical outcome in 67 pancreatic cancer patients treated with cisplatin and S-1 or with S-1 alone. ERCC1 codon 118 polymorphism was analyzed using PCR-RFLP. Thirty-nine of the patients (58.2%) were homozygous for AAC codon, 7 (10.4%) were homozygous for AAT codon, and 21 (31.3%) were heterozygous. Among those treated with cisplatin and S-1, no significant difference in objective response rate was observed between genotypes. However, the patients with one or two AAT codons had a significantly longer progression-free survival (PFS) and overall survival (OS) than those homozygous for AAC allele (PFS: 338 days vs 106 days, p=0.006, OS: 763 days vs 415 days, p=0.030). In contrast, no significant difference in PFS or OS was observed between genotypes among the patients treated with S-1 alone. ERCC1 polymorphism may be a useful prognostic marker in patients with pancreatic cancer treated with platinum-based chemotherapy.