Background: RAS and BRAF mutations are associated with lack of response to anti-EGFR therapy and worse survival in patients with metastatic colorectal cancer (mCRC). NRAS mutations are less frequent than KRAS and BRAF mutations. While the prognostic implication of BRAF V600E mutations in mCRC is well established, the impact of NRAS mutations on outcome is unclear. Methods: Patients with mCRC who had RAS/RAF mutations tested at Mayo Clinic and MD Anderson Cancer Center between 2012 and 2016 were included in this study. Clinical information was obtained by chart review, and clinical characteristics and survival outcomes were compared among patients with different mutations. Categorical data were analyzed by Chi-square test, and time-to-event data were analyzed by Kaplan-Meier and Cox proportional hazards models. Statistical analysis was done in SPSS (v22). Results: In 2953 patients (1076 from Mayo and 1877 from MD Anderson), the mutation frequencies were: KRAS 45.6%, NRAS 3.8%, BRAF V600 8.0% and BRAF non-V600 1.3% (all wild-type [WT] 41.3%). 2282 patients with sufficient clinical information available were included for survival analysis, including 951 WT (41.7%), 1080 KRAS (47.3%), 91 NRAS (4.0%) and 160 BRAF V600 (7.0%). Compared with WT, NRAS patients were more likely female (47% vs 36%, P= 0.031) and had more right-sided cancers (30% vs 20%, P= 0.031). NRAS and KRAS patients did not differ in age, sex, sidedness, or MSI-H/dMMR. Compared with BRAF, NRAS patients were younger ( < 60, 59% vs 44%, P= 0.018), had more left-sided cancers (70% vs 29%, P< 0.001), and had less MSI-H/dMMR (1% vs 17%, P= 0.001). The median follow-up was 42.7 months. The median overall survival (OS) for WT, KRAS, NRAS and BRAF patients were 49.2, 36.2, 30.1 and 22.5 months, respectively (P< 0.001). In multivariate analysis adjusting for age, sex and sidedness, NRAS patients had worse OS than WT (HR = 1.83 [1.40-2.39], P< 0.001) and KRAS patients (HR = 1.37 [1.06-1.78], P= 0.016). The OS difference between NRAS and BRAF patients was not statistically significant (HR = 0.81 [0.57-1.14], P= 0.220). Conclusions:KRAS, NRAS and BRAF mutations have distinct impacts on survival in mCRC. NRAS mutations carry a poorer prognosis compared with KRAS.