Abstract: Objective To explore the safety and efficacy of different dissection level of para-aortic lymph nodes in the patients with endometrial cancer (EC). Methods This study was a prospective follow-up study which included subjects with endometrial cancer between January 1, 2010 and December 31, 2015. These subjects were divided into inferior mesenteric artery (IMA) group and renal vein (RV) group randomly. The para-aortic lymph nodes were dissected to the level of inferior mesenteric artery and the renal vein in the IMA group and the RV group, respectively. The intraoperative and postoperative complications were recorded. The main form of follow-up was telephone follow-up. Follow-up endpoint was cancer recurrence. Kaplan-Meier method was used to estimate survival rate. The survival difference between the two groups was compared using the log-rank test. Results There was no significant difference in the incidence of intraoperative complications and postoperative complications between the two groups (χ²=0.110, 0.107; P=0.740, 0.744). A total of 49 cases relapsed in the both groups. Twenty-nine and 20 patients relapsed in the IMA group and the RV group, respectively. Kaplan-Meier curve didn't show the difference between the two groups. A total of 20 cases relapsed in Ⅰ stage patients in the both groups. Eleven and 9 patients relapsed in the IMA group and the RV group, respectively. Kaplan-Meier curve didn't show the difference between the I stage subjects in the two groups.A total of 29 cases relapsed in Ⅱ-Ⅳ stage patients in the both groups. Eighteen and 11 patients relapsed in the IMA group and the RV group, respectively. Kaplan-Meier curve showed the significant difference between the Ⅱ-Ⅳ stage subjects in the two groups. Conclusion Para-aortic lymph node dissection to the level of renal vein is safe and effective, especially in patients with advanced endometrial cancer, which can help to reduce tumor recurrence and improve long-term prognosis.