Modern desistance research has examined many facets of desistance, both in terms of theoretical predictors of desistance and recidivism, and in terms of differing types of offending. Though predicting desistance from illegal drug use is among these topics, no research to date has examined the predictors of desisting from prescription opioid abuse. This study uses longitudinal data from 318 prescription opioid users to analyze the effects of various predictors of desistance on declining nonmedical prescription opioid use, with an emphasis on gender differences among participants. Results indicate theoretical and demographic characteristics correspond with differing rates of decline and further vary by gender.