BackgroundOptimising HIV pre-exposure prophylaxis (PrEP) provision requires insight into preferences of PrEP regimens and PrEP discontinuation. We assessed regimen switching and discontinuation and their determinants among men who have sex with men (MSM) participating in the Amsterdam PrEP demonstration project.MethodsBetween 3-August-2015 and 31-May-2016, we enrolled MSM (n = 374) and TGP (n = 2) in a prospective, longitudinal study. Participants could choose between daily or event-driven PrEP regimens at enrolment and every 3 months. We assessed transition intensities (TI) and determinants of switching (i) between regimens, and (ii) from either regimen to discontinuing PrEP using a multi-state Markov model. PrEP discontinuation was defined as formally stopping study participation or having no study visit for ≥6 months.FindingsOf 367 analysed participants, 73·3% chose daily and 26·7% event-driven PrEP at enrolment. Median follow-up was 3·1 years (IQR 2·9–3·2). 121 participants switched their PrEP regimen at least once (cumulative probability 34·2%, 95% CI 29·4–39·6), with 90 switches from event-driven to daily PrEP (TI 0·35/PY, 95% CI 0·29–0·44) and 113 switches from daily to event-driven PrEP (TI 0·16/PY, 95% CI 0·13–0·20). Switching from event-driven to daily PrEP was associated with younger age, not reporting sex with HIV-positive partners, chemsex, and sexual compulsivity. Switching from daily to event-driven PrEP were associated with younger age and lower sexual satisfaction. 67 participants discontinued PrEP (cumulative probability 17·7%, 95% CI 14·1–22·2), with no difference between regimens: event-driven (n = 23, TI 0·08/PY, 95% CI 0·05–0·13) and daily PrEP (n = 44, TI 0·06/PY, 95% CI 0·04–0·08). Discontinuing daily PrEP was associated with younger age, fewer casual partners, and higher number of condomless anal sex acts with casual partners.InterpretationSwitching between PrEP regimens was common, while going from event-driven to daily PrEP use was associated with certain sexual-related determinants (i.e. chemsex, sexual compulsivity, no known HIV-positive partners). PrEP discontinuation rates were low and independent of regimens. PrEP care should consider the reasons for choice and switch of regimen and involve education on safely switching or discontinuing PrEP, especially among younger MSM. FundingZonMw, H-TEAM, RIVM, GGD research funds, Aidsfonds, Amsterdam Diner Foundation, Gilead Sciences, Gilead Sciences Europe Ltd, Janssen Pharmaceuticals, MAC AIDS Fund, ViiV Healthcare.