ObjectiveTo compare the effects of minimally invasive surgery (MIS) and open surgery (OPS) on the risk of recurrence and mortality in patients with endometrial cancer (EC) of high-risk histology (grade 3 endometrioid adenocarcinoma, papillary serous carcinoma [PS], clear cell carcinoma [CC], and carcinosarcoma) using meta-analysis. Material and methodsWe systematically reviewed published studies comparing MIS and OPS in EC patients with high-risk histology until January 2022. The endpoints were recurrence and mortality rate. Study design features that may have affected participant selection, recurrence/death detection, and manuscript publication were assessed. For pooled estimates of the effect of MIS on recurrence/mortality, the random- or fixed-effects meta-analytical models were used after assessing the cross-study heterogeneity. ResultNine observational studies (eight retrospective and one prospective) fulfilled our search criteria (MIS, 8877 patients; OPS, 5751 patients). The fixed-effects model-based meta-analysis indicated that MIS did not significantly increase the risk of recurrence (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.71–1.05; p = 0.13) and mortality (HR, 0.86; 95% CI, 0.79–0.93; p < 0.001) when compared with OPS. This pattern was also observed in the subgroup analyses based on the stage (early stage vs. all stage), histology (PS and CC), and MIS type (laparoscopy vs. robotic). There was no evidence of publication bias. ConclusionThis meta-analysis of observational studies revealed that MIS did not compromise the prognosis of EC patients with high-risk histology. Well-designed randomized controlled trials could verify the results of this uncommon but deadly tumor.