Background: Reducing HIV transmission using pre-exposure prophylaxis (PrEP) requires targeting individuals at high acquisition risk, such as men who have sex with men (MSM) with a history of non-occupational post-exposure prophylaxis (nPEP). This study aims to characterize longitudinal trends in PrEP uptake and its determinants among nPEP users in Montreal. Methods: Eligible attendees at Clinique medicale l Actuel were recruited prospectively starting in October 2000 (nPEP) and January 2013 (PrEP). Linking these cohorts, we characterized the PEP-to-PrEP cascade, examined the determinants of PrEP uptake after nPEP consultation using a Cox proportional-hazard model, and assessed whether PrEP persistence differed by nPEP history using Kaplan-Meier curves. Results: As of August 2019, 31% of 2,682 MSM nPEP cohort participants had two or more nPEP consultations. Subsequent PrEP consultations occurred among 36% of nPEP users, of which 17% sought nPEP again afterwards. Among 2,718 PrEP cohort participants, 46% reported previous nPEP use. Among nPEP users, those aged 25-49 years (Hazard Ratio (HR)=1.3, 95% confidence interval (CI): 1.1-1.7), with more nPEP episodes (HR=1.4, 95%CI: 1.3-1.5), reported chemsex (HR=1.3, 95%CI: 1.1-1.7), with a STI history (HR=1.5; 95%CI: 1.3-1.7), and who returned for their first nPEP follow-up visit (HR=3.4, 95%CI: 2.7-4.2) had higher rates of PrEP linkage. There was no difference in PrEP persistence between PEP-to-PrEP and PrEP only participants. Conclusion: Over one-third of nPEP users were subsequently prescribed PrEP. However, the large proportion of men who repeatedly use nPEP calls for more efficient PrEP-linkage services and, among those that use PrEP, improved persistence should be encouraged.