Objective: This article models the cost-effectiveness, from a societal viewpoint, of a dental caries prevention program using salt fluoridation for children 12 years of age, compared with non-intervention (or status quo) in Arequipa, Peru. Methods: Standard cost-effectiveness analysis methods were used. The costs associated with implementing and operating the salt-fluoridation program were identified and measured using 2009 prices. Health outcomes were measured as dental caries averted over a 6-year period. Clinical effectiveness data was taken from published data. Costs were measured as direct treatment costs, programs costs and costs of productivity losses as a result of dental treatments. The incremental cost-effectiveness ratio was calculated. A hypothetical population of 25,000 12-year-olds living in Arequipa, Peru was used in this analysis. Two-way sensitivity analyses were conducted over a range of values for key parameters. Results: Our primary analysis estimated that if a dental caries prevention program using salt-fluoridation was available for 25,000 6-year-old children for 6 years, the net saving from a societal perspective would total S/. 11.95 [1 US$ = S/. (2009) 3.01] per diseased tooth averted when compared with the status quo group. That is, after 6 years, an investment of S/.0.32 per annum per child would result in a net saving of S/.11.95 per decayed/missing/filled teeth prevented. Conclusions: While the analysis has inherent limitations as a result of its reliance on a range of assumptions, the findings indicate that for the situations prevailing in Peru, there are significant health and economic benefits to be gained from the use of salt fluoridation.