Prospective, population-based cohort study. To examine whether prescription of opioids within 6 weeks of low back injury is associated with work disability at 1 year. Factors related to early medical treatment have been little investigated as possible risk factors for development of long-term work disability among workers with back injuries. We have previously shown that about 1 of 3 of workers receive an opioid prescription early after a low back injury, and a recent study suggested that such prescriptions may increase risk for subsequent disability. We analyzed detailed data reflecting paid bills for opioids prescribed within 6 weeks of the first medical visit for a back injury among 1843 workers with lost work-time claims. Additional baseline measures included an injury severity rating from medical records, and demographic, psychosocial, pain, function, smoking, and alcohol measures from a worker survey conducted 18 days (median) after receipt of the back injury claim. Computerized database records of work disability 1 year after claim submission were obtained for the primary outcome measure. Nearly 14% (254 of 1843) of the sample were receiving work disability compensation at 1 year. More than one-third of the workers (630 of 1843) received an opioid prescription within 6 weeks, and 50.7% of these (319 of 630) were received at the first medical visit. After adjustment for pain, function, injury severity, and other baseline covariates, receipt of opioids for more than 7 days (odds ratio = 2.2; 95% confidence interval, 1.5-3.1) and receipt of more than 1 opioid prescription were associated significantly with work disability at 1 year. Prescription of opioids for more than 7 days for workers with acute back injuries is a risk factor for long-term disability. Further research is needed to elucidate this association.