Background: Microsatellite instability (MSI) phenotype is found in approximately 12% of colorectal cancers (CRC). MSI CRC is associated with a low recurrence rate and 5-fluorouracil chemoresistance in adjuvant setting. Clinical and pathological prognostic factors of recurrence are well-identified after surgery of CRC but not in the subgroup of MSI CRC. Methods: This multicenter retrospective study included patients with stage I, II and III MSI CRC. The following prognostic factors were studied: age, sex, perforation, occlusion, tumor location, tumor differentiation, T4 stage, lymph node invasion, VELIPI criteria (vascular emboli, lymphatic invasion and perinervous invasion), BRAF mutation and adjuvant chemotherapy. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. Prognostic factors of DFS were analyzed in multivariate analysis using Cox model. Results: A total of 294 MSI CRC patients were analyzed, including 10%, 49% and 41% stage I, II and III, respectively. Mean age was 67.2 ± 16.0 years. Occlusion was observed in 10% of cases. VELIPI criteria were found in 39%, including 26% with vascular emboli. BRAF mutation was detected in 27% of cases. All in all, 40% of patients received adjuvant chemotherapy, predominantly stage III (74%). Mean follow-up was 39.2 ± 33.2 months. The disease recurrence rate was 3%, 8% and 21% in stage I, II and III patients, respectively. The 3-year DFS rate was 85%. In univariate analysis, age, occlusion, lymph node invasion, T4 stage, vascular emboli and perinervous invasion were associated with decreased DFS (p<0.05). In multivariate analysis, only occlusion (RR=3.0; 95% CI 1.2-7.7, p=0.02) and vascular emboli (RR=4.5; 95% CI 1.6-12.7, p<0.01) were associated with decreased DFS. Recurrence rates for MSI CRC with and without vascular emboli were respectively, 22% versus 5% for stage II and 33% versus 15% for stage III. Conclusions: Occlusion and vascular emboli were independently associated with recurrence of MSI CRC but not lymph node invasion. We advocate vascular emboli analysis in routine clinical practice to facilitate adjuvant chemotherapy decision-making in MSI CRC.