Background: Human Immunodeficiency Virus (HIV) is a global public health threat, and all frontline Health care workers (HCWs) are at a higher risk of exposure to body fluids from potential HIV patients and to sharp instruments. Though timely Post Exposure Prophylaxis (PEP) decreases the possibility of seroconversion to HIV after occupational exposure, most HCWs rarely adhere to the PEP protocol. This study aims to determine the predictors of adherence to PEP among frontline healthcare workers in the Ho Teaching Hospital, Ghana. Methods: A facility-based cross-sectional study was conducted among 199 frontline HCWs. Data were collected using a pretested self-administered questionnaire and analyzed using STATA version 14 software. Binomial logistic regression was performed at the 0.05 level of significance and 95% confidence interval. Findings: Overall, 17.9% of HCWs adhered to PEP. Frontline HCWs who perceived they had low and very low risk of occupational exposure to HIV transmission were 96% [AOR = 0.04 (95% C.