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DNA mismatch repair (MMR) status was considered to be a potential prognostic factor for colorectal cancer (CRC) but with conflicting reports, and varied in terms of TNM stages. Its relationship with prognosis in stage II‐III CRC had not yet been systematically established. Therefore, we retrieved eligible studies published through May 2019, and screened out 51 studies that reported survival data (overall survival [OS] and/or disease‐free survival [DFS]) in 28 331 CRC patients at stage II‐III, totally 16.4% of whom were characterized as deficient MMR (dMMR). Significant associations of dMMR status were observed with longer OS (Hazard Ratio [HR] = 0.74, 95% CI: 0.68‐0.82; P <.001), as well as DFS (HR = 0.67, 95% CI: 0.59‐0.75, P <.001). However, dMMR patients received no statistically significant benefit from fluoropyrimidine‐based treatment for either OS (HR = 0.84, 95%CI: 0.60‐1.17; P =.31) or DFS (HR = 0.83, 95%CI: 0.60‐1.15; P =.27), compared with that in proficient MMR (pMMR) patients for both OS (HR = 0.55, 95% CI: 0.43‐0.71; P <.001) and DFS (HR = 0.60, 95% CI: 0.50‐0.73; P <.001). Our analysis indicate that dMMR CRC patients at stage II‐III had higher OS and DFS than pMMR ones, and fluoropyrimidine‐based chemotherapy could improve survival in pMMR patients rather than dMMR ones. [ABSTRACT FROM AUTHOR]