Compliance with infection prevention and control (IPC) protocols is critical in minimizing the risk of coronavirus disease (COVID-19) infection among healthcare workers. However, data on IPC compliance among healthcare workers in COVID-19 treatment centers are unknown in Ghana. This study aims to assess IPC compliance among healthcare workers in Ghana's COVID-19 treatment centers. The study was a secondary analysis of data, which was initially collected to determine the level of risk of COVID-19 virus infection among healthcare workers in Ghana. Quantitative data were conveniently collected using the WHO COVID-19 risk assessment tool. We analyzed the data using descriptive statistics and logistic regression analyses. We observed that IPC compliance during healthcare interactions was 88.4% for hand hygiene and 90.6% for Personal Protective Equipment (PPE) usage; IPC compliance while performing aerosol-generating procedures (AGPs), was 97.5% for hand hygiene and 97.5% for PPE usage. For hand hygiene during healthcare interactions, lower compliance was seen among nonclinical staff [OR (odds ratio): 0.43; 95% CI (Confidence interval): 0.21-0.89], and healthcare workers with secondary level qualification (OR: 0.24; 95% CI: 0.08-0.71). Midwives (OR: 0.29; 95% CI: 0.09-0.93) and Pharmacists (OR: 0.15; 95% CI: 0.02-0.92) compliance with hand hygiene was significantly lower than registered nurses. For PPE usage during healthcare interactions, lower compliance was seen among healthcare workers who were separated/divorced/widowed (OR: 0.08; 95% CI: 0.01-0.43), those with secondary level qualifications (OR 0.08; 95% CI 0.01-0.43), non-clinical staff (OR 0.16 95% CI 0.07-0.35), cleaners (OR: 0.16; 95% CI: 0.05-0.52), pharmacists (OR: 0.07; 95% CI: 0.01-0.49) and among healthcare workers who reported of insufficiency of PPEs (OR: 0.33; 95% CI: 0.14-0.77). Generally, healthcare workers' infection prevention and control compliance were high, but this compliance differs across the different groups of health professionals in the treatment centers. Ensuring an adequate supply of IPC logistics coupled with behavior change interventions and paying particular attention to nonclinical staff is critical in minimizing the risk of COVID-19 transmission in the treatment centers.