Health care workers are the most affected part of the world population due to the COVID-19 pandemic. Countries prioritize vaccinating health workers against COVID-19 because of their susceptibility to the virus. However, the acceptability of the vaccine varies across populations. Thus, this study aimed to determine the health care worker's intentions to accept the COVID-19 vaccine and its associated factors in southwestern Ethiopia, 2021. A facility-based cross-sectional study was conducted among health care workers in public hospitals in southwestern Ethiopia from March 15 to 28, 2021. A simple random sampling method was used to select 405 participants from each hospital. Data were collected using self-administered questionnaires. Descriptive statistics, such as frequency and percentage, were calculated. Multivariable logistic regression was also performed to identify factors associated with health care worker's intention to accept the COVID-19 vaccine. Statistically significant variables were selected based on p-values (<0.05) and the adjusted odds ratio was used to describe the strength of association with 95% confidence intervals. Among the respondents, 48.4% [95% CI: 38.6, 58.2] of health care workers intended to accept COVID-19. Intention to accept COVID-19 vaccination was significantly associated with physicians (AOR = 9.27, 95% CI: 1.27-27.32), professionals with a history of chronic illness (AOR = 4.07, 95% CI: 2.02-8.21), perceived degree of risk of COVID-19 infection (AOR = 4.63, 95% CI: 1.26-16.98), positive attitude toward COVID-19 prevention (AOR = 6.08, 95% CI: 3.39-10.91) and good preventive practices (AOR = 2.83, 95% CI: 1.58-5.08). In this study, the intention of health care workers to accept the COVID-19 vaccine was low. Professional types, history of chronic illness, perceived degree of risk to COVID-19 infection, attitude toward COVID-19 and preventive practices were found to be factors for intention to accept COVID-19 vaccine in professionals. It is important to consider professional types, history of chronic illness, perceived degree of risk to COVID-19, attitude of professionals and preventive behaviors to improve the intention of professionals' vaccine acceptance.