BACKGROUND Exposure to blood and bodily fluids represents a significant occupational risk for nurses. The most effective means of preventing bloodborne pathogen transmission is through adherence to Standard Precautions (SP). Despite published guidelines on infection control and negative health consequences of noncompliance, significant issues remain around compliance with SP to protect nurses from bloodborne infectious diseases, including hepatitis B virus, hepatitis C virus (HCV), and HIV. METHODS A descriptive correlational study was conducted that measured self-reported compliance with SP, knowledge of HCV, and perceived susceptibility and severity of HCV plus perceived benefits and barriers to SP use. Relationships between the variables were examined. Registered nurses (N = 231) working in ambulatory settings were surveyed. RESULTS Fewer than one-fifth (17.4%) of respondents reported compliance with all 9 SP items. Mean score for correct responses to the HCV knowledge test was 81%. There was a significant relationship between susceptibility of HCV and compliance and between barriers to SP use and compliance. CONCLUSIONS This study explored reasons why nurses fail to adopt behaviors that protect them and used the Health Belief Model for the theoretical framework. It concentrated on SP and HCV because more than 5 million people in the United States and 200 million worldwide are infected with HCV, making it 1 of the greatest public health threats faced in this century. Understanding reasons for noncompliance will help determine a strategy for improving behavior and programs that target the aspects that were less than satisfactory to improve overall compliance. It is critical to examine factors that influence compliance to encourage those that will lead to total compliance and eliminate those that prevent it.