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Introduction Men who have sex with men (MSM) are disproportionately affected by HIV due to their increased risk of infection. Oral pre-exposure prophylaxis (PrEP) is a highly effictive HIV-prevention strategy for MSM. Despite evidence of its effectiveness, PrEP uptake in the United States has been slow, in part due to its cost. As jurisdictions and health organizations begin to think about PrEP scale-up, the high cost to society needs to be understood. Methods We modified a previously-described decision-analysis model to estimate the cost per quality-adjusted life-year (QALY) gained, over a 1-year duration of PrEP intervention and lifetime time horizon. Using updated parameter estimates, we calculated: 1) the cost per QALY gained, stratified over 4 strata of PrEP cost (a function of both drug cost and provider costs); and 2) PrEP drug cost per year required to fall at or under 4 cost per QALY gained thresholds. Results When PrEP drug costs were reduced by 60%(with no sexual disinhibition) to 80%(assuming 25% sexual disinhibition), PrEP was cost-effective (at< 100,000perQALYaverted)inallscenariosofbase-caseorbetteradherence,aslongasthebackgroundHIVprevalencewasgreaterthan10%.ForPrEPtobecostsavingatbase-caseadherence/efficacylevelsandatabackgroundprevalenceof20%,drugcostwouldneedtobereducedto 8,021 per year with no disinhibition, and to 2,548withdisinhibition.ConclusionResultsfromouranalysissuggestthatPrEPdrugcostsneedtobereducedinordertobecost-effectiveacrossarangeofbackgroundHIVprevalence.Moreover,ourresultsprovideguidanceonthepricingofgenericemtricitabine/tenofovirdisoproxilfumarate …