Background: Royal Marsden Hospital prognostic Index (RMH-I), which was based on performance status, ALP, liver metastasis and peritoneal metastasis, was reported as prognostic factor of advanced esophago-gastric cancer before first line chemotherapy (Chau I, et al. J Clin Oncol 22:2395-2403, 2004). Usefulness of RMH-I in second line chemotherapy is not elucidated. Methods: Advanced gastric cancer patients who started second line chemotherapy in Hokkaido University Hospital from July 2001 to May 2013 with prior fluoropyrimidine plus platinum administration were retrospectively analyzed. Univariate and multivariate analysis for overall survival were performed using patient characteristics (RMH-I, hemoglobin, CRP, CEA, Alb, TTP in first line, primary lesion resection, and bone metastasis). Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 77 eligible patients. Male/Female were 52/25, median age was 60 years (range 31-80) and unresectable/recurrent were 70/7. Median survival was 7.1 months. The distribution and median survival for RMH-I groups were as follows: good risk (n = 8), 8.2 months; moderate risk (n = 57), 9.6 months; and poor risk (n = 12), 4.4 months. Although poor risk group showed shorter survival time, there were not significant difference regardless of RMH-I in Cox multivariate analysis (HR 1.12, 95%CI 0.61-2.09, P=0.72). Conclusions: In this retrospective analysis, RMH-I was not independent prognostic factor in second line chemotherapy of advanced gastric cancer. Prognostic factors in this population need to be investigated further.