Healthcare workers (HCWs) are at risk of contracting coronavirus disease-2019 (COVID-19) in their workplace. Infection prevention guidelines and standard operating procedures were introduced to reduce risk of exposure and prevent transmission. Safe practices during interaction with patients with COVID-19 are crucial for infection prevention and control (IPC). This study aimed to assess HCWs' compliance to IPC and to determine its association with sociodemographic and organizational factors. A cross-sectional study was conducted between March and April 2021 at public healthcare facilities in the east coast of Peninsular Malaysia. HCWs who were involved with COVID-19-related works were invited to participate in the online survey. The questionnaire was adapted from the World Health Organization (WHO) Interim Guidance: WHO Risk Assessment and Management of Exposure of Healthcare Workers in the Context of COVID-19. Respondents were categorized as compliant or non-compliant to IPC. A total of 600 HCWs involved in COVID-19-related works participated in the survey. Most of them (63.7%) were compliant to IPC as they responded to all items as "always, as recommended" during interaction with patients with COVID-19. The multivariate analysis showed that non-compliance was significantly associated with working in the emergency department (AOR = 3.16; 95% CI = 1.07-9.31), working as laboratory personnel (AOR = 15.13; 95% CI = 1.36-168.44), health attendant (AOR = 4.42; 95% CI = 1.74-11.24), and others (AOR = 3.63; 95% CI = 1.1-12.01), as well as work experience of more than 10 years (AOR = 4.71; 95% CI = 1.28-17.27). The odds of non-compliance among respondents without adequate new norms and personal protective equipment training were 2.02 (95% CI = 1.08-3.81) more than those with adequate training. Although most of the respondents complied to IPC protocols, compliance status differed according to department, work category, and years of service. Ensuring adequate training that will hopefully lead to behavioral change is crucial to prevent breach in IPC and thus minimize the risk of exposure to and transmission of COVID-19 in healthcare facilities.