OBJECTIVES: We sought to determine sex-specific associations between experiences of physical pain, pain management, and frequency of nonmedical prescription opioid (NMPO) use among young adults. METHODS: Among participants enrolled in the Rhode Island Young Adult Prescription Drug Study, we identified associations between physical pain in the past 6 months, pain history, pain management, polysubstance use, and weekly NMPO use. In sex-specific models, independent correlates of weekly NMPO use were identified via modified stepwise Poisson regression. RESULTS: Of 199 participants, the mean age was 24.6, and 65.3% were male. The racial composition was 16.6% black, 60.8% white, and 22.1% mixed or other race. A total of 119 (59.8%) participants reported weekly or greater NMPO use. The majority of male (86.2%) and female (84.1%) participants reported ever experiencing severe pain. A majority of males (72.3%) and females (81.2%) reported that they engaged in NMPO use to treat their physical pain, and one-quarter (26.9%) of males and one-third (36.2%) of females had been denied a prescription from a doctor to treat severe pain. Among males, frequent NMPO use was independently associated with white race (P < 0.001) and reporting greater physical pain (P = 0.002). Among females, older age (P = 0.002) and monthly or greater nonmedical benzodiazepine use (P = 0.001) were independently associated with weekly NMPO use. CONCLUSIONS: Among young men in Rhode Island, physical pain may be related to frequent NMPO use. More research is needed to identify sex-specific, pain-related factors that are linked with NMPO use to improve harm reduction and pain management interventions.