OBJECTIVES: We assess the tradeoffs between the costs and benefits of choosing alternate HIV prevention strategies, including the status-quo (current HIV testing with antiretroviral therapy [ART] initiation at CD4 ≤500), testing (expanded HIV testing with ART initiation at CD4 ≤500), test-and-treat (expanded HIV testing and early ART start), and PrEP (PrEP initiation by uninfected individuals) strategies. METHODS: A mathematical epidemiological model is developed to simulate HIV incidence among 15-65 year old MSM in LAC. An economic model uses the epidemic model results to estimate the cost and effectiveness of 624 variants of the testing, test-and-treat and PrEP strategies from a societal perspective. For each strategy, we estimate the number of new HIV infections averted, the discounted costs and quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratios. The sensitivity and robustness of the estimates are assessed via univariate and bootstrapping probabilistic sensitivity analyses. RESULTS: In the base case analysis, test-and-treat, PrEP, and testing are highly cost-effective relative to status-quo ($21 000, $26 000, and $27 500/QALY) and significantly reduce new infections. This is imputable to the preventive benefits of PrEP and early knowledge of infection status via testing, and the survival gains from early ART initiation. Thirteen strategies consisting of more aggressive test-and-treat and PrEP approaches trace the efficient frontier for decision making. More aggressive strategies are more costly but yield better effectiveness profiles, albeit with diminishing returns. These results remain generally robust to uncertainty in the epidemic, cost, and effectiveness parameters. The relative effectiveness of PrEP is however sensitive to PrEP and ART adherence and initiation rates. CONCLUSIONS: PrEP and test-and-treat strategies are cost-effective alternatives to the status-quo for HIV prevention among LAC MSM. When affordable, aggressive combinations of these strategies should be implemented. The effectiveness of these strategies could be enhanced with greater adherence to ART and PrEP.