For a study, researchers sought to evaluate the efficacy of minimally invasive surgery (MIS) versus open surgery (OPS) in reducing the risk of recurrence and death from endometrial cancer (EC) in patients with high-risk histology (grade 3 endometrioid adenocarcinoma, papillary serous carcinoma [PS], clear cell carcinoma [CC], and carcinosarcoma). Studies comparing MIS and OPS for high-risk histology EC patients published until January 2022 were analyzed comprehensively. The rates of recurrence and mortality were the cutoffs. Researchers looked at potential participant selection, recurrence/death detection, and manuscript publishing biases in the study design. After accounting for cross-study variability, researchers employed random- or fixed-effects meta-analytical models to compile estimates of MIS’s impact on recurrence/mortality. Researchers found 9 observational studies that met their criteria; 8 were retrospective, and 1 was prospective (MIS, 8877 patients; OPS, 5751 patients). After accounting for confounding factors, the meta-analysis based on a fixed-effects model found that MIS did not significantly increase the risk of recurrence (hazard ratio [HR], 0.86; 95% CI, 0.71-1.05; P=0.13) or death (HR, 0.86; 95% CI, 0.79-0.93; P<0.001). This trend was also seen in subgroup analyses stratified by stage (early stage vs. all stage), histology (PS and CC), and MIS type (laparoscopy vs. robotic). The data did not support publication bias. Based on this meta-analysis of observational studies, MIS does not negatively impact the prognosis of patients with EC with high-risk histology. Only well-planned randomized controlled trials can confirm the findings of this rare but lethal tumor.