Background: Medical waste handlers are at immediate risk of needle stick injuries and exposure to infectious materials from medical waste. Adequate knowledge and safe practices on the part of the workers are essential for the prevention of nosocomial infections. Objective: To assess and compare the factors involved in occupational risk prevention practices among medical waste handlers in two tertiary hospitals in Ogun State, Nigeria. Methods: This descriptive, cross-sectional study compared medical waste handlers and the risk prevention measures available in a specialist hospital and a teaching hospital. The 100 participants were randomly selected and surveyed using an interviewer-administered questionnaire. Results: The prevalence of needle stick injury at the teaching hospital and specialist hospital were 38% and 28%, respectively. Hepatitis B vaccine uptake was 6% in the teaching hospital compared to 70% at the specialist hospital. There was a significant difference concerning the provision of safety equipment (p<0.001), personal protective equipment (PPE) (p<0.001), Hepatitis vaccine (p<0.001), training (p<0.001) and availability of waste management policy (p = 0.015) but no significant difference concerning the regular supply of water and soap (p = 0.494) between both institutions. Conclusion: The waste handlers at the specialist hospital were better equipped for safety than those at the teaching hospital. A safer environment, equipment, and training for medical waste handlers are needed to enable them to practise occupational risk prevention more effectively.