Background: Enzyme powders inhaled at workplace can induce respiratory allergy in health care workers. It is important to elucidate which risk factors contribute to the sensitization of these enzymes in health care workers. Objective: This study evaluates the prevalence and the risk factors of sensitization to pancreatic enzyme powders in health care workers. Method: A total of 220 health care workers (199 nurses and 21 pharmacist`s office workers) who were exposed to pancreatic enzyme powders during work and 64 unexposed controls (office workers) in a single hospital were analyzed using a questionnaire, and measurements of total serum IgE level and specific IgE against house dust mite and the most popular pancreatic enzymes (α-amylase and pancreatin). Result: The overall prevalence of sensitization to pancreatic enzymes was 4.7%. Sensitization to pancreatic enzymes is significantly higher in pharmacist`s office workers (28.6%) than in controls (0%) or nurses (5.0%). In multivariate analysis, occupational exposure (OR, 25.5; 95% CI, 5.7∼113.5), and elevated total IgE level (OR, 6.95; 95% CI, 1.6∼28.9) were associated with sensitization to pancreatic enzymes. Conclusion: Occupational exposure and elevated serum IgE level may be important determinants of sensitization to pancreatic enzymes in health care workers. Measures to reduce exposure may be the most effective means to reduce sensitization. (Korean J Asthma Allergy Clin Immunol 2009;29:21-26)