Background: Optimal breastfeeding is among the best and effective ways to promote optimal development of children in early childhood. Recent estimates suggested that optimal breastfeeding could prevent around 12% of deaths in under-5 children every year, representing around 800,000 lives in low- and middle-income countries. Objectives: The aim of this study was to assess the prevalence of optimal breastfeeding practice and associated factors among mothers of children 24-36 months of age in Tehuledere District, North East Ethiopia, 2020. Methods: A community-based cross-sectional study was conducted among 522 mothers of children 24-36 months of age from March 01-26/2020. Systematic random sampling technique was used to select the study participants. Interviewer administered structured questionnaire was used to collect data from the study participants. The data was entered using epi data version 3.1 and analyzed by using Statistical Packages for Social Sciences (SPSS) version 20.0. Bivariable and multivariable logistic regression analyses were computed. Results: Five hundred twenty-two study participants had participated in the study yielding the response rate of 99%. The prevalence of optimal breastfeeding was 44.3% (95% CI=40.1, 48.1). Access to media (AOR=2.547[95% CI=1.203, 5.395]), having male child (AOR=2.697[95% CI=1.492, 4.874]), child birth weight < 2.5 kg (AOR=4.864[95% CI=1.240, 19.080]) and 1-3 times antenatal care (ANC) visits (AOR=.282[95% CI=.154, .518]) were the factors significantly associated with optimal breastfeeding practice. Conclusions: In this study, the prevalence of optimal breastfeeding practice was low. Access to media, sex of the child, weight of the child and number antenatal care visits were significantly associated. Key words: Children, Optimal Breastfeeding practice, Mothers, Tehuledere District