Introduction: - Inconsistent use of antiretroviral therapy poses the risk of cross-resistance across the drugs. This narrows the subsequent regimen alternatives. As evidences showed that the magnitude of initial antiretroviral therapy regimen change in children has been highly important. However, the incidence and predictors of initial regimen change in the study setting has been limited. Objective: - This study was aimed to assess incidence and predictors of initial antiretroviral therapy regimen change among children in public health facilities of Bahir Dar city. Methods and Materials: - A retrospective follow up study was conducted among 485 children who were on antiretroviral therapy from January 1, 2011 to December 30, 2020. These children were selected by a simple random sampling technique. The data were entered by Epi data 3.1 and analysis was done by STATA 14.0. The missing data was treated with multiple imputation method. The data were also summarized by median, interquartile range, proportion and frequency. The survival time was determined using the Kaplan Meier curve. The Cox Proportional Hazard model was fitted to identify predictors of initial antiretroviral therapy regimen change. The global and Shoenfeld graphical proportional hazard test was checked. Any statistical test was considered significant at P-value < 0.05. Finally, the data were presented using tables, graphs and text forms. Result: - From 459 study participants, 315 of them experienced initial regimen changes within the accrual period of the study. The minimum and maximum follow up of the study was 1 month and 118 months, respectively. The overall incidence rate of initial regimen change was 1.85, 95% CI (1.66-2.07) per 100 person-month observation with a median follow up time of 49 (IQR 45, 53) months. The independent predictors of initial regimen change were poor adherence (AHR=1.49, 95%CI [1.16, 1.92]), NVP based regimen (AHR=1.45, 95%CI [1.15, 1.84]), history of tuberculosis (AHR=1.59, 95%CI [1.14, 2.23]), ART initiation after 2017 (AHR=5.26, 95%CI [3.49, 7.92]) and being male (AHR=1.28, 95%CI [1.02, 1.60]). Conclusion and recommendations: - In this study, the incidence of initial regimen change was high. The initial regimen change was predicted by sex, adherence, history of tuberculosis and the initial regimen type. Therefore, strengthening adherence counseling, tuberculosis screening and prevention counseling and care of initial regimen type choice needs attention in the care and treatment of HIV/AIDS. Keywords: - Children, human immunodeficiency virus, Antiretroviral therapy, initial regimen change, Bahirdar city.