The cumulative risk of human immunodeficiency virus (HIV) infection over a healthcare career has rarely been estimated, but is more relevant to the description of an occupational hazard than the risk of seroconversion from a single exposure. We describe a model for assessing the individualized risk for HIV infection after multiple potential exposures over many years for surgeons and other operating room personnel, a high-risk group. For the average surgeon operating over a 30-year career on patients with an HIV seroprevalence of 0.01, the cumulative risk is estimated at 1%. The same surgeon operating on patients with a seroprevalence of 0.10 has an estimated cumulative risk of 10%. These risks may vary dramatically depending on the assumed rate of skin punctures during surgery. Healthcare workers need to be aware of the cumulative risk from multiple exposures to infectious blood and body fluids, to follow proposed suggestions for the reduction of percutaneous blood exposures and to assist in developing new technology to further reduce these risks. Failure to protect these professionals could result in the reduction of services for the approximately 1 to 1.5 million HIV-infected persons in the United States.