To reappraise pre-exposure prophylaxis (PrEP) eligibility criteria towards the men who have sex with men (MSM) with highest HIV-risk, we assessed PrEP need (i.e. HIV-risk) using Amsterdam Cohort Studies data from 2011–2017 for all non-PrEP using MSM. Outcomes were incident HIV-infection and newly-diagnosed anal STI. Determinants were current PrEP eligibility criteria (anal STI and condomless sex (CAS)) and additional determinants (age, education, group sex, alcohol use during sex and chemsex). We used targeted maximum likelihood estimation (TMLE) to estimate the relative risk (RR) and 95% confidence intervals (CI) of determinants on outcomes, and calculated population attributable fractions (PAFs) with 95% CI using RRs from TMLE. Among 810 included MSM, 22 HIV-infections and 436 anal STIs ( n = 229) were diagnosed during follow-up. Chemsex (RR = 5.8 (95% CI 2.0–17.0); PAF = 55.3% (95% CI 43.3–83.4)), CAS with a casual partner (RR = 3.3 (95% CI 1.3–8.7); PAF = 38.0% (95% CI 18.3–93.6)) and anal STI (RR = 5.3 (95% CI 1.7–16.7); PAF = 22.0 (95% CI −16.8 to 100.0)) were significantly ( P < 0.05) associated with and had highest attributable risk fractions for HIV. Chemsex (RR = 2.0 (95% CI 1.6–2.4); PAF = 19.5 (95% CI 10.6–30.6)) and CAS with a casual partner (RR = 2.5 (95% CI 2.0–3.0); PAF = 28.0 (95% CI 21.0–36.4)) were also significantly associated with anal STI, as was younger age (16–34/≥35; RR = 1.7 (95% CI 1.4–2.1); PAF = 15.5 (95% CI 6.4–27.6)) and group sex (RR = 1.3 (95% CI 1.1–1.6); PAF = 9.0 (95% CI −2.3 to 23.7)). Chemsex should be an additional PrEP eligibility criterion.