BACKGROUND: Pre-exposure prophylaxis (PrEP) medicines are key to reducing HIV infection. Improving access, increasing initiation, and expanding the populations covered is therefore important. In June, 2021, in France, PrEP initiation was extended to primary care. The aim of this study was to describe the deployment and characteristics of PrEP initiation in primary care. METHODS: We did a nationwide cohort study using data obtained from the French National Health Data System (Systeme National des Donnees de Sante). We included all people aged 15 years or older, who initiated PrEP in primary care between June 1, 2021, and Dec 31, 2022. We estimated the number of PrEP initiations per month over the period, and the characteristics of people initiating PrEP and prescribers, and PrEP use. FINDINGS: 13 500 individuals initiated PrEP in primary care during the study period. The mean number of PrEP initiations increased from 654 (SD 64) per month between July and December, 2021, to 783 (SD 86) per month between July and December, 2022. Individuals initiating PrEP were predominantly male (12 996 [96.3%] of 13 500 individuals) with a mean age of 36 years (SD 11.8), who lived in large urban areas (9581 [71.0%]). 1012 (7.5%) of 13 500 individuals were socioeconomically disadvantaged. Of the 5125 PrEP initiation prescribers, 4542 (88.6%) were general practitioners (GPs), and 4713 (44.7%) of 10 525 were the patient's family practitioner. In the 6 months after PrEP initiation, 6216 (70.8%) of 8783 PrEP initiators had at least one monthly renewal (mean 3.3 renewals [SD 1.7]). 11 961 (82.4%) of 14 507 renewals were made by the same practitioner who had initiated PrEP, and this proportion was higher when the prescriber who had initiated PrEP was the family practitioner (6225 [92.5%] of 7135 renewals). INTERPRETATION: Although the number of PrEP initiations in primary care steadily increased over the study period, the profile of users was unchanged when compared with before extension. The high proportion of PrEP initiations not prescribed by family practitioners highlights potential barriers to sharing sexual health concerns with the family practitioner. Extending PrEP to women, individuals who are socioeconomically disadvantaged, and all those who might benefit from it will require increased awareness among target audiences and practitioners. FUNDING: French National Agency for Medicines and Health Products Safety.< Réduire