Introduction/objective(s) The paper aims to describe oral preexposure prophylaxis (PrEP) initiations and discontinuations among female sex workers (FSWs) in Côte d’Ivoire, and to elaborate broader considerations about their perceptions, through barriers and facilitators of PrEP use. Methods The ANRS 12381 PRINCESSE project provides a comprehensive sexual and reproductive healthcare package, including PrEP, among a cohort of FSWs aged ≥18 years in the San Pedro region. This package is offered in a community clinic and through a mobile clinic operating on 10 prostitution sites (visited every two weeks) for 45 months (12/2019-06/2023). The analysis is based on qualitative interviews with 38 FSWs conducted in December 2019, September 2021, March and May 2022, and clinical records related to PrEP use filled out by the physicians. Results Interviews showed that many women identified the protective effect of PrEP against HIV despite sometimes being afraid of side effects. Few women reported perceiving no benefit of PrEP compared to condoms. End-February 2023, 406 HIV- and HBV-negative women were included : 388 (96%) declared their interest in PrEP. Among them, 218 (56%) exited care within 6 weeks, 4 were not interested in PrEP anymore, and only 165 (43%) initiated PrEP. In interviews, some women explained having stopped PrEP immediately because of side effects. Some women also reported having stopped PrEP after a few weeks because of their difficulties in taking a daily treatment at a fixed time. FSWs also shared that a major reason for PrEP discontinuation is related to periods of mobility when they leave to visit their families and no longer work. These women sometimes re-initiated PrEP, but not immediately after starting sex work again. Among the 165 FSWs who initiated PrEP, 60 (36%) attended their first PrEP follow-up visit, of whom 16 (27%) reported having discontinued PrEP. Among the latest, 4 (25%) reported not being interested anymore. The other 12 and the 44 who did not discontinue PrEP received a second prescription. At each subsequent visit of PrEP follow-up, a part of the women reported PrEP discontinuation, and some decided to stop PrEP. More broadly, the confidence in PrEP is not total among women interviewed. Some reported rumours and fear of being identified as HIV-positive among colleagues. Others used simultaneously other means to protect against HIV, such as enema after condomless sex, because PrEP is taken once a day and not after each intercourse. Discussion/conclusion/implications Although loss to follow-up was a major issue, it was not the only barrier to PrEP initiation and retention. Despite high levels of interest in PrEP, PrEP discontinuation was frequent, partly linked to periods of mobility. Oral daily PrEP is not a magic bullet : it sometimes appears difficult for FSWs to articulate PrEP with other daily priorities. FSWs regularly evaluate the balance between constraints and benefits at each step of the process. In this specific population of FSWs, there is an urgent need to find new ways of simplifying HIV biomedical prevention.