The risks and benefits of postexposure rabies prophylaxis were analyzed from clinical and economic perspectives. A decision-analytic model was constructed by using probability and outcome data from the literature and the state health department. Health outcomes were measured in quality-adjusted life years. In the base case (overweight adult male), treatment is optimal when the probability of animal rabidity is greater than 1 in 2000. Sensitivity analysis showed robustness in the treatment decision; however, the incremental cost-effectiveness ratio ($140,000/quality-adjusted life year) is sensitive to the rabidity probability. Treatment is optimal from the patient's perspective; however, it may not be cost-effective when the probability of rabidity is low.