BackgroundGlobally, Coronavirus disease-19 has created unprecedented challenges to public health. Healthcare workers (HCWs) are at risk of COVID-19 because of their profession. There are limited studies conducted in Ethiopia among HCWs regarding their compliance with COVID-19 preventive measures. Therefore, this study intended to assess HCWs’ compliance with measures to prevent COVID-19, and its potential determinants in public hospitals in Western Ethiopia.MethodsA self-administered, multicenter hospital-based cross-sectional survey was proposed to 422 randomly selected HCWs working in seven public hospitals in Western Ethiopia identified as COVID-19 referral centers. Data were entered into Epi Data version 3.1 and analyzed using SPSS version 24. Binary logistic regression was used to identify potential determinants of outcome variables at p-value < 0.05.ResultsOut of 422 completed questionnaires, the overall HCWs’ compliance with COVID-19 prevention is 22% (n = 404). In multivariate regression analysis, factors such as spending most of caring time at bedside (AOR = 1.94, 95%CI, 1.06–3.55), receiving training on infection prevention/COVID-19 (AOR = 1.86, 95%CI, 1.04–3.33), reading materials on COVID-19 (AOR = 2.04, 95%CI, 1.14–3.63) and having support from hospital management (AOR = 2.09, 95%CI, 1.20–3.64) were found to be significantly associated with COVID-19 preventive measures. Furthermore, inadequate supplies of appropriate personal protective equipment (83.2%), insufficient supportive medications (78.5%), and lack of provision of adequate ventilation (77.7%) were the barriers to COVID-19 prevention most frequently mentioned by participants.ConclusionOur findings highlight HCWs’ poor compliance with COVID-19 preventive measures. Providing information and refreshing training to improve the level of healthcare workers’ adherence with COVID-19 prevention is as imperative as increasing staff commitment to supply resources necessary to protect HCWs and to reduce healthcare-associated infections transmission of SARS-COV-2.