To evaluate the impact of increased access restrictions to branded oxycodone hydrochloride extended-release tablets (oxycodone HCl ER), on healthcare utilization and costs in patients using extended-release and long-acting opioids (ER/LA opioids) from the health plan perspective during the period from 1/1/2009 to 6/30/2012. This retrospective cohort study analyzed claims data for adult patients from US plans that increased oxycodone HCl ER access restrictions. Study groups were segmented into commercial and Medicare payers, and by prior authorization (PA) and tier change (TC) restrictions. Six-month outpatient visits and prescription utilization and costs were evaluated during the pre- and post-access restriction periods using a bootstrapped t-test and regression to test the differences. Mean 6-month post-restriction combined pharmacy and outpatient visit costs were $1131 (p < 0.001), $660 (p = 0.009), $699 (p < 0.001), and $564 (p < 0.001) higher than pre-restriction costs in commercial PA, commercial TC, Medicare PA, and Medicare TC groups, respectively. Outpatient visits accounted for the greatest proportion of increased costs in the access restriction groups. The results of this study suggest that oxycodone HCl ER access restrictions such as PA and TC may increase medical costs without an offsetting savings in pharmacy costs.