OBJECTIVE: To evaluate the effectiveness of various medications for the treatment of endometriosis-related pain through a network meta-analysis. DATA SOURCES: A comprehensive search was conducted in PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register until July 22, 2024. We also searched ClinicalTrials.gov for additional data on recently completed trials or potentially eligible randomized controlled trials (RCTs) but found nothing. METHODS OF STUDY SELECTION: The analysis included randomized RCTs that used pharmacologic interventions for managing endometriosis-related pain. The primary efficacy outcome was endometriosis-associated pelvic pain, which included dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain. The analysis adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. TABULATION, INTEGRATION, AND RESULTS: A total of 31 RCTs involving 8,665 patients were included in the analysis. In terms of endometriosis-associated pelvic pain, four interventions demonstrated significantly greater efficacy compared with placebo: leuprolide combined with combined oral contraceptive pills (OCPs) (standardized mean difference [SMD] -1.40, 95% CI, -2.41 to -0.38), dienogest (SMD -1.20, 95% CI, -1.78 to -0.61), leuprolide alone (SMD -1.05, 95% CI, -1.64 to -0.45), and combined OCP (SMD -0.67, 95% CI, -1.25 to -0.09). Leuprolide combined with combined OCP emerged as the most effective treatment modality. In addition, elagolix and the combination of vitamin C and vitamin E were identified as the most effective interventions for dysmenorrhea and dyspareunia. For nonmenstrual pelvic pain, gestrinone demonstrated superior efficacy compared with placebo and all other interventions. CONCLUSION: This network meta-analysis indicates that leuprolide in combination with combined OCP, elagolix, vitamins C and E, and gestrinone may represent the most effective therapeutic options for alleviating endometriosis-associated pelvic pain, dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain. These findings enhance our understanding of the relative efficacy of treatment strategies for pain associated with endometriosis. Future research should focus on conducting larger-scale and rigorously designed clinical trials within the target patient populations to further validate these results.