Men who have sex with men (MSM) who experience problematic chemsex are at high risk of acquiring HIV due to combined drug use and sexual behaviours. Pre-exposure prophylaxis (PrEP) could substantially reduce the risk of HIV transmission in this group of men. The aim of this study was to examine the biopsychosocial characteristics associated with PrEP use among HIV-negative MSM who have experienced problematic chemsex. This was a cross-sectional analysis of secondary data collected during client assessments at a specialist alcohol and drug service based within the United Kingdom. We compared the socio-demographics, substance use, sexual behaviours and mental health of MSM who reported ever using PrEP to those who reported never using PrEP. Statistical analysis was conducted using the Mann–Whitney U-test for continuous variables and Fisher’s exact test for categorical variables. Between August 2016 and July 2018, 165 HIV-negative MSM who engaged in chemsex had an assessment completed. Thirty-four per cent (n = 50/145) had ever used PrEP. The median age was 36 years (IQR: 30–42), 92% identified as gay (n = 152/165) and 79% were of white ethnicity (n = 130/164). The use of crystal methamphetamine was associated with higher levels of men ever using PrEP (40% versus 21%) (p= 0.047). Men who had ever used PrEP had a higher median number of sexual partners in the previous three months (20 versus 10) (p= 0.004) and had lower level of condom use in their sex lives (median reported 5% versus 50%) (p= 0.010) in comparison to men who had never used PrEP. It is encouraging that men having higher-risk sex had been accessing PrEP. However, further research is required to explore PrEP uptake, retention and adherence in this high-risk group.