Objectives: A high prevalence of viral hepatitis B and C was found among healthcare workers during a province-wide screening in Sindh Province, Pakistan. A follow-up study was undertaken to identify risk factors for this high prevalence in healthcare workers. Design: Population based case–control design. Setting: Public sector healthcare facilities in a rural district of Pakistan. Participants: Healthcare workers who were screened for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibodies. 178 healthcare workers employed at the public sector clinics and hospitals of the district were approached, of which 14 refused to participate. Cases had detectable serum antibodies against HCV and the presence of HBsAg. Healthcare workers non-reactive to HCV antibodies and with no HBsAg were controls. These were matched in a ratio of 1:1. Outcome measure: Detectable serum HBsAg and HCV antibody titer were taken as outcome. OR for various exposures was calculated; those with p<0.25 were entered in a multivariate logistic regression model to find out significant predictors. Results: Needle stick injury (OR=6; CI95 1.4 to 23), recapping the needle (OR=5.7; CI95 1.1 to 28), wound care at accident and emergency of a hospital (OR=5.5; CI95 1 to 28), female gender (OR=3.4; CI95 1 to 12) and more than 10 years of formal education (OR=0.25; CI95 0.07 to 0.8) were associated with hepatitis C. Hepatitis B was found to be associated with trying to bend or break a needle after use (OR=4.9; CI95 1 to 24). Conclusions: Healthcare workers in Pakistan are at additional risk of exposure to bloodborne pathogens. Bi-dimensional risk factors present at individual and broader health systems levels are responsible. Occupational safety, health trainings and redesigning of the curriculum for allied health professionals are required.