BackgroundImplementing standard precautions (SP) has been a major challenge for health care workers (HCWs) especially those in developing countries thereby compromising their safety and increasing their exposure to blood-related pathogens. Compliance with safety precautions and occupational accidents among health workers are often unreported. The literature on knowledge and compliance to SP in Ghana is scanty. We report findings of a study that examined knowledge of SP, compliance and barriers to compliance with SP among HCWs in two health facilities in Ghana.MethodsThis is a facility-based cross-sectional study involving 100 HCWs from two health facilities in the Lower Manya Krobo District of the Eastern region. Statistical analysis summarised data on socio-demographic characteristics of respondents, knowledge of SP and compliance and barriers to SP in frequencies and percentages.ResultsMost respondents had been working as health staff for 0–5 years (65.0%). Generally, knowledge of the basic concepts of SP was low; only 37.0% of HCWs knew that SP includes hand washing before and after any direct contact with the patient, 39.0% knew about cough etiquettes and 40.0% knew about aseptic techniques which involve infection prevention strategies to minimise the risks of infection. Fifty percent of respondents always protect themselves against BBFs of patients. About a quarter of the respondents do not recap needles after use and 28.0% of respondents sometimes promptly wipe all blood spills. HCWs were of the opinion that wearing PPEs—such as gloves, aprons, gowns and goggles—might cause patients to panic sometimes (63.0%) and complying with SP sometimes interferes with the ability to provide care (38.0%). Sometimes, because of the demands of patient care, HCWs do not have enough time to comply with the rigours of SP (44.0%) and sometimes PPEs are not available.ConclusionEducation programmes on the benefits of SP should be organised frequently. The OHS national policy together with the application of the IPC training manual in all health care facilities must be enforced. Communities of practice should be established and sanctions and rewards should be introduced to limit negative behavior and reinforce positive attitudes as regards SP.