Abstract Background In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. Methods Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. Results From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50\,years\:=\:1.76, 95% CI 1.35\textendash 2.3, P\:<\:0.001) and site of prescription (OR of former IPERGAY sites\:=\:2.28, 95% CI 1.84\textendash 2.83, P\:<\:0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR\:=\:0.68, 95% CI 0.57\textendash 0.82 and 0.75, 95% CI 0.57\textendash 0.98, respectively; P\:<\:0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. Conclusions In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.