The Occupational Safety and Health Administration proposed a vaccination program for workers exposed to the hepatitis B virus 12 or more times per year. We performed a benefit-cost analysis of the proposed regulation and an expanded rule that covers all at-risk workers, regardless of the number of exposures. The annualized cost of the proposed vaccination program is estimated at $60.4 million. We estimated the dollar benefit of the program using two methods. The first estimates the avoided cost of medical care, prophylaxis, and lost productivity at $124 million annually. The second approach includes the value of avoided pain and suffering from hepatitis B, thus increasing the total dollar benefit to $679 million. Although both methods indicate benefits are greater than program costs, the valuation of avoided pain and suffering substantially increases net benefits. Furthermore, providing the vaccine to all exposed workers is cost-effective if one or more cases of hepatitis B are avoided per 6500 workers annually.