Background: A pilot study of GS showed good results with median TTP of 10.0 months and OS of 20.4 months in unresectable PC (Oncology.2009;77:300-3). The aim of this study was to compare GS combination therapy to G monotherapy (UMIN-CTR 000000498). The first analysis at September 2009 showed significantly longer progression-free survival in GS (5.4 months) than in G (3.6 months) (presented at ASCO 2010). Overall survival was analyzed in this final analysis. Methods: Patients (pts) were randomized 1:1 to G (gemcitabine 1,000 mg/m² 30min i.v. day 1, 8, 15, repeated every 4 weeks) or to GS (G 1,000 mg/m² 30 min i.v. day1, 15 and S-1 40 mg/m² p.o. twice daily days 1-14, every 4 weeks). Eligible pts had unresectable locally advanced or metastatic pancreatic cancer without any prior treatment and ECOG PS 0-2. Results: Between July 2006 and February 2009, 106 pts were enrolled in 6 hospitals. At the time of this final analysis, 2 pts in G and 4 pts in GS were still alive. The median age, 67 and 63, male, 62% and 79%, PS=0, 60% and 58%, locally advanced, 25% and 28% in G and GS, respectively. S-1 was introduced as second line chemotherapy in 58% patients after failure of G. Median OS was 8.8 months (95%CI, 7.0-10.6) in G and 13.5 month (95%CI, 7.8-16.3) in GS (HR 0.72, 95%CI 0.48-1.07, p=0.104), and 1-year survival rate was 30.2% in G and 52.8% in GS (p=0.031). Conclusions: The addition of S to G demonstrated significantly higher 1-year survival rate with 4.7 months increase in median OS. Though this increase in survival was not statistically significant because of the small sample size, GS may be the standard chemotherapy in advanced pancreatic cancer.