Background: Healthcare waste management (HCWM) system in healthcare facilities is essential in dealing with the spread of infectious diseases, especially during an outbreak period such as the COVID-19 pandemic. The study assessed health care waste management situation in selected healthcare facilities in the greater Accra and Ashanti regions of Ghana during the COVID-19 pandemic.Methods: This was a multi-facility-based cross-sectional study that used a monitoring tool of the health facilities regulatory agency of Ghana to collect information on health care waste management practices at the peak of the COVID-19 pandemic. Data was gathered from 501 healthcare facilities in the greater Accra (335) and Ashanti (151) regions. Descriptive, Chi-square and multiple logistic regression were performed. All statistical analyses were considered significant at an alpha level of 0.05.Results: Less than half (45.7%) of the health facilities were assessed as having HCWM systems with majority (54.3%) having effective infectious waste management system. The health facilities in the greater Accra region (38.8%) and Ashanti region (60.9%) were categorized as poor on healthcare waste management system. The assessment levels of governance/leadership, management, quality assurance system, human resource, infection prevention and control equipment and water management were all significantly associated with the adherence to good HCWM systems.Conclusions: Health facilities were assessed as having good healthcare waste management systems, especially in the greater Accra region compared to the Ashanti, however treatment and safe disposal should be improved.