To identify the prevalence of opioid use in individuals with chronic spinal cord injury (SCI) living in South Carolina. Cohort study. Data from 2 statewide population-based databases, an SCI Registry and the state prescription drug monitoring program, were linked and analyzed. The study included individuals (N=503) with chronic (>1y) SCI who were injured between 2013 and 2014 in South Carolina and who survived at least 3 years postinjury. Not applicable. Filled opioid prescriptions over a 2-year period (months 13-36 after injury). The main outcomes were total number of days with an opioid prescription over the 2-year period, length of coverage period [(final day of prescription coverage+the days supplied)-first day of prescription coverage], average daily morphine milligram equivalents (MME) over the coverage period, and concurrent days covered by an opioid and a prescription for benzodiazepines, sedatives, or hypnotics. A total of 53.5% of the cohort (269 individuals) filled at least 1 opioid prescription during their second or third year after SCI. In total, there were 3386 opioid fills during the 2-year study. On average, the total number of opioid prescription days was 293±367. The average coverage period was 389±290 days, and the average daily MME during the coverage period was 41±70 MME. Of those who filled an opioid prescription, 23% had high-risk fills (>50 MME), and 38% had concurrent prescriptions for benzodiazepines, sedatives, or hypnotics. The prevalence of opioid use was high among individuals with chronic SCI, exceeding rates observed in the general population. Also concerning were the rates of high-risk fills, based on average daily MME and concurrent benzodiazepine, sedative, or hypnotic prescriptions. These findings, taken together with those of earlier studies, should be used by providers to assess and monitor opioid use, decrease concurrent high-risk medication use, and attenuate the risk of adverse outcomes. Copyright © 2020. Published by Elsevier Inc.