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Men who have sex with men (MSM) who have a current or recent history of rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection are at greater risk for HIV than MSM with no history of rectal infection. Screening and treating MSM for rectal CT/GC infection may help reduce any increased biological susceptibility to HIV infection.We used 2 versions of a Markov state-transition model to examine the impact and cost-effectiveness of screening MSM for rectal CT/GC infection in San Francisco: a static version that included only the benefits to those screened and a dynamic version that accounted for population-level impacts of screening. HIV prevention through reduced susceptibility to HIV was the only potential benefit of rectal CT/GC screening that we included in our analysis. Parameter values were based on San Francisco program data and the literature.In the base case, the cost per quality-adjusted life year gained through screening MSM for rectal CT/GC infection was $16,300 in the static version of the model. In the dynamic model, the cost per quality-adjusted life year gained was less than $0, meaning that rectal screening was cost-saving. The impact of rectal CT/GC infection on the risk of HIV acquisition was the most influential model parameter.Although more information is needed regarding the impact of rectal CT/GC screening on HIV incidence, rectal CT/GC screening of MSM can potentially be a cost-effective, scalable intervention targeted to at-risk MSM in certain urban settings such as San Francisco.