There are considerable new data on mutation topography in persons with myelodysplastic syndromes (MDS). These data have been used to update conventional risk models such as the Revised International Prognostic Scoring System (IPSS-R). Whether the molecular IPSS (IPSS-M) which includes these data improves survival prediction accuracy is untested. To answer this question, we compared survival prediction accuracies of the IPSS-R and IPSS-M in 852 consecutive subjects with de novo MDS. Concordance statistics (C-statistics) of the IPSS-R and IPSS-M in the entire cohort were similar, 0.67 (95% Confidence Interval [CI] 0.64, 0.71) and 0.68 (0.64, 0.71). Average numbers of mutations and of IPSS-M related mutations were greater in persons ≥ 60 years (2.0 [Interquartile Range [IQR], 1, 3] vs. 1.6 [0, 2], P = 0.003; 1.6 [0, 2] vs. 1.3 [0, 2], P = 0.006). Subjects ≥ 60 years had a higher incidence of mutations in RUNX1, TP53, TET2, SRSF2, DNMT3A, STAG2, EZH2 and DDX41. In contrast, mutations in U2AF1 were more common in persons < 60 years. Next we tested survival prediction accuracy based on age < or ≥ 60 years. C-statistics of the IPSS-R and IPSS-M in subjects ≥ 60 years were 0.66 (0.61, 0.71) and 0.69 (0.64, 0.73) whereas in subjects < 60 years they were 0.67 (0.61, 0.72) and 0.65 (0.59, 0.71). These data indicate an advantage for the IPSS-M over the IPSS-R in subjects ≥ 60 years but not in those < 60 years probably because of a great frequency of mutations correlated with survival in those ≥ 60 years.