OBJECTIVE: To compare the performance of matching-adjusted indirect comparison (MAIC) and naïve indirect comparison (NIC) under a wide range of data scenarios on survival outcome. METHODS: A simulation study included 729 (3 RESULTS: MAIC yielded relatively unbiased estimates of relative treatment effect compared with NIC in most scenarios, with better coverage and MSE but higher ESE. None of the situational variables had a significant impact on the bias and coverage of MAIC. However, increasing IPD sample size and covariate overlap significantly reduced the ESE and MSE of MAIC. In scenarios with low covariate overlap and high covariate strength, the bias of MAIC was larger and even greater than that of NIC. CONCLUSIONS: The performance of MAIC consistently demonstrates advantage over NIC across various scenarios. MAIC often provides more unbiased estimates and achieves confidence interval coverage close to nominal values compared with NIC. While MAIC may exhibit higher ESE in specific scenarios, this additional uncertainty can offer a more accurate reflection of variability, enhancing the robustness of the results. Researchers should thoroughly comprehend the influencing factors and interactions affecting the performance of these methods and judiciously apply research findings.