Background: Many people with sexually transmitted diseases (STDs) in Lima, Peru, seek treatment in pharmacies. Goal: The goal was to assess the cost-effectiveness of training pharmacy workers in syndromic management of STDs. Study Design: Cost-effectiveness from both the program and societal perspectives was determined on the basis of study costs, societal costs (cost of medicine), and the number of cases adequately managed. The latter was calculated from estimated incidence, proportion of symptomatic patients, proportion seeking treatment in pharmacies, and proportion of cases adequately managed in both comparison and intervention districts. Univariate and multivariate sensitivity analyses were performed. Results: Under base-case assumptions, from the societal perspective the intervention saved an estimated US$1.51 per case adequately managed; from the program perspective, it cost an estimated US$3.67 per case adequately managed. In the sensitivity analyses, the proportion of females with vaginal discharge or pelvic inflammatory disease who seek treatment in pharmacies had the greatest impact on the estimated cost-effectiveness, along with the medication costs under the societal perspective. Conclusion: Training pharmacists in syndromic management of STDs appears to be cost-effective when only program costs are used and cost-saving from the societal perspective. Our methods provide a template for assessing the cost-effectiveness of managing STD syndromes, on the basis of indirect estimates of effectiveness.