Twenty per cent of new HIV infections in the USA arise in young men (aged 13–24 years) who have sex with men (YMSM); however, >50% of YMSM with HIV do not know their HIV status. Mathematical simulation was used to assess clinical benefit and cost-effectiveness of yearly, 6-monthly and 3-monthly screening strategies, in addition to the status quo (SQ), in high-risk YMSM aged from 15 years. Published data (YMSM-specific when available) were used for the model and projected outcomes included CD4 count at diagnosis, primary HIV transmissions from age 15–30 years, quality-adjusted life expectancy, costs and incremental cost-effectiveness ratios. All strategies increased projected CD4 at diagnosis and quality-adjusted life expectancy from age 15 compared with SQ, and also increased discounted lifetime cost for the entire population. Screening at 3-monthly intervals was cost-effective compared with SQ and reduced primary transmissions by 40% in YMSM aged up to 30 years.