Three treatment regimens are currently recommended for penicillin-susceptible Neisseria gonorrhoeae infection of the cervix: ampicillin, tetracycline, and a combination of ampicillin and tetracycline. To evaluate the cost-effectiveness of these options, we developed a decision analysis model and analyzed the efficacy of each treatment in curing gonorrhea, as well as coexisting Chlamydia trachomatis infection, and in preventing subsequent pelvic inflammatory disease, ectopic pregnancy, and infertility. We included direct costs of medication and expenditures for management of unresolved infections and associated complications. Combination treatment is more than twice as cost-effective as tetracycline and seven times as cost-effective as ampicillin when the medical cost of managing pelvic inflammatory disease is considered. When the costs of ectopic pregnancies and infertility are included, the cost-effectiveness of combination treatment increases further.