Background: The major complications of pelvic inflammatory disease (infertility, ectopic pregnancy, and chronic pelvic pain) are the leading cause of non-HIV sexually transmitted disease morbidity in the United States. Goal: The goal of the study was to estimate a plausible range for the average lifetime cost of pelvic inflammatory disease (PID) and its major complications in a cohort of U.S. women of reproductive age. Study Design: We developed a state-transition computer-based model to simulate the natural history of PID, incorporating the severity of infection, number of recurrent episodes, treatment setting, and the risk over time of major complications. Clinical and cost data were from the published literature. Model outcomes included life expectancy, quality-adjusted life expectancy, and lifetime costs. Results: In a cohort of 100,000 females acquiring PID between 20 and 24 years of age, 8550 ectopic pregnancies, 16,800 cases of infertility, and 18,600 cases of chronic pelvic pain were projected to occur. Assuming a 3% annual discount rate, we found the average per-person lifetime cost to be $2150. Average lifetime costs for women who developed major complications were $6350 for chronic pelvic pain, $6840 for ectopic pregnancy, and $1270 for infertility. The majority of costs (79%) were accrued within 5 years of upper genital tract infection. Results were most sensitive to assumptions about the timing of major complications and the discount rate. Conclusion: The average per-person lifetime cost of PID ranges between $1060 and $3180. Future cost-effectiveness analyses of STD screening programs can include this range as a reasonable upper and lower bound. These findings suggest successful PID prevention efforts may avert substantial costs for care providers such as managed care organizations while providing well documented clinical benefits for women in the United States.