AbstractIntroductionIllicit drug use while admitted to hospital is common amongst people who use drugs. Furthermore, non‐medical prescription opioid use (NMPOU) is increasingly being used by this population. This study was undertaken to investigate the relationship between NMPOU and having ever reported using illicit drugs in the hospital.MethodsThis study was a cross‐sectional study design based on data derived from participants enrolled in three Canadian prospective cohort studies between December 2011 and November 2016. Using bivariable and multivariable logistic regression analyses, we examined the relationship between NMPOU and having ever reported illicit drug use in the hospital.ResultsAmong the 1865 participants (951 male, 471 female) enrolled in the studies, 1422 (76.25%) met the inclusion criteria of having ever been hospitalised. Of these, 436 (30.7%) had used illicit drugs while in the hospital. In multivariable analyses, after adjusting for various confounders, we found a positive relationship between the percentage of reporting at least daily NMPOU in the past 6 months during the cohort study period and illicit drug use in the hospital (adjusted odds ratio 3.42; 95% confidence interval 1.46–8.02).Discussion and ConclusionsAmong our sample, more persistent NMPOU was positively associated with having reported in‐hospital illicit drug use. Our findings point to the need for better identification and management of opioid use disorder in acute care settings to reduce in‐hospital illicit drug use, and to offer evidence‐based medical treatments to achieve the most optimal outcomes for patients.