Background- Thousands of millions of people fall ill as a result of eating unsafe food and in the prevalence of food borne disease many die due to less knowledge and practice on the part of food handlers. Food handlers play an important role in ensuring food handling practice throughout the chain of production, processing, storage and preparation. Objectives-To assess food handling practice and associated factors among food handlers work in food and drink establishments’ of South Achefer district, North West Ethiopia 2019. Methods– Institutional based cross sectional study was conducted from october15- 30/2019. All food and drink establishments and all food handlers work in the establishments of South Achefer district was included in the study; that means 394 food handlers and 156 foods and drink establishments was included. Data was collected from each food handler’s by direct interviewing and observation of their personal hygiene. The data was checked, coded and entered to EPI-INFO version 3.5.3 and was exported to SPSS version 20 for analysis. Descriptive statistics to describe study objectives and bivariable and multivariable logistic regression analysis done used to identify factors associated with food handling practice. Odd ratio with 95% CI and p- value < 0.05 was computed to measure the strength of association and significance level. Results- A total 394 food handlers were participated with 100% response rate. The total prevalence of good food handling practice was 212(53.8%). And food handlers had good knowledge score was 261(66.2%). Age (AOR: 0.382, 95% CI 0.159- 0.919), educational status (AOR: 0.306, 95% CI 0.108- 0.871) & (AOR: 0.512, 95% CI 0.289- 0.909), knowledge of food handlers (AOR: 0.241, 95% CI 0.131- 0.443) and sanitary inspection and supervision (AOR: 0.203, 95% CI 0.118- 0.350) were the factors significantly associated with food handling practices. Conclusion and Recommendation-The current study reveals that relatively low good food handling practice was observed. Age, education, knowledge, sanitary inspection and supervision were significantly associated with food handling practice, therefore needs continues sanitary inspection should be performed regularly on food handler’s general personal hygiene practice, and also beater education also needed. Keywords- Food handling practices, Food Handlers, South Achefer district