This article examines the relative importance of occupational, epidemiologic, and attitudinal factors in hepatitis B vaccine acceptance. A stratified random sample of 1,018 health care workers at risk for occupational blood exposure at our university hospital were contacted in 1992 and 919 (90%) participated. Potential reasons for vaccine acceptance or refusal were evaluated with factor analysis. Logistic regression models were calibrated on a stratified random subsample to identify independent predictors of initiating and completing the series, then validated on the remaining subjects. Fifty-four percent (482 of 898) of previously nonimmune workers had completed the series, while 70% (626) had received one or more doses. Hepatitis B vaccine acceptance was related strongly to social influence (physicians, supervisors, role models, friends, and spouse) and knowledge of the disease and vaccine, whereas refusal was primarily related to concern about vaccine side effects and problems with vaccine access. Independent predictors of initiating the vaccine series included younger age (odds ratio [OR] 0.98 per year, 95% confidence interval [CI95] 0.96-0.997), occupation (housestaff: OR 2.9, CI95 1.1-7.9; nurses: OR 2.1, CI95 1.0-4.3 versus housekeepers), increased blood exposure frequency (OR 2.4, CI95 1.6-3.5 for 1-6 versus 0 exposures in past year), and increased frequency of recent influenza vaccination (OR 3.3, CI95 2.0-5.3 for 1 versus 0 doses in prior 3 years). Occupation (increased acceptance among housestaff, nurses, nursing assistants, laboratory technicians), increased frequency of blood exposure, and recent influenza vaccination also were predictors of series completion. Factors such as occupation, blood exposure frequency and acceptance of other preventive services may help identify health care worker groups with low vaccine acceptance most likely to benefit from targeted vaccine delivery. Hepatitis B vaccine should be offered routinely during evaluation for occupational blood exposure. Future vaccine implementation efforts should emphasize the involvement of physicians and supervisors and education about occupational disease risk, liability, and the safety of the vaccine.