Background: Human immunodeficiency virus is the public health issue that affects the health of an individual through reducing body’s immune system. Despite, antiretroviral therapy could reduce the transmission of human immunodeficiency virus and related morbidity, loss to follow up is a main challenge among human immunodeficiency virus infected children. Objective:The aim of this study was to assess the incidence and predictors of loss to follow up among under 15 years old children on highly active antiretroviral therapy at Dessie referral hospital, North east Ethiopia, 2020. Methods: A ten year institution based retrospective cohort study was employed among 448 under 15 years’ old children who were enrolled on antiretroviral therapy. Data were entered and cleared using Epi- data version 3.1 and then exported to STATA version 14 for further statistical analysis. Kaplan Meier survival curve was used to estimate the survival time and log rank test was used to compare the survival time between different categories of the explanatory variables. Scaled schoenfeld residual test was used to check proportional hazard assumption. Multivariable Cox proportional hazards model was fitted to identify predictors of loss to follow up and p-value < 0.05 was considered as statically significant. Results: The overall incidence rate of loss to follow up was 6.3 per100 children in years of observation. Being male (AHR=2.1, CI =1.37 ,3.34), age 1-5 years (AHR=1.6,CI=1.05,2.46), poor adherence to antiretroviral therapy (AHR = 6.6 ; CI=4.11,10.66), fair adherence to antiretroviral therapy (AHR= 2.2 ; CI = 1.13 ,4.20), regimen was not changed (AHR = 4.1 ; CI = 2.59 ,6.45 ),world health organization stage III and IV (AHR= 2.2 ; CI =1.40, 3.33) and heightfor age < -2 z score ( AHR = 2.2; CI = 1.43 , 3.44) were predictors of loss to follow up. Conclusion: The incidence rate of loss to follow was high. Age 1-5 years, world healthorganization stage III and IV, poor and fair adherence to antiretroviral therapy, regimen was not changed, being male and stunted were higher risk for loss to follow up. Therefore, close monitoring to the higher risk groups for loss to follow up high lighted in this study could decrease the rate of loss to follow up. Improving the adherence of children to antiretrioviral therapy and nutritional support for stunted children were also recommended. Keywords: Incidence, Predictors, Loss to follow up, Ethiopia