OBJECTIVES: To assess pill burden, healthcare resource utilization (HRU), and costs among patients with long-term immediate release (IR) hydrocodone use. METHODS: We performed a retrospective analysis of healthcare claims from 2011-2012 Truven MarketScan® Commercial, Medicare supplemental, and Medicaid Multistate databases. Patients with IR hydrocodone prescription for ≥ 90 days during 6 month baseline period (July 2011- December 2011) with continuous enrollment during baseline and 12 month follow-up periods were selected. The final population was sub-categorized by prescribed coverage days (PCD) of IR hydrocodone during baseline into 90-119, 120-179, and ≥180 days. Chi-square or ANOVA analyses were used to test pill burden, HRU and costs (standardized to 2013 US dollars) during baseline and follow-up periods across subpopulations. RESULTS: A total of 36,174 commercial, 32,699 Medicaid, and 8,873 Medicare IR hydrocodone users were selected.  In the baseline period, subgroups with longer PCD had significantly more average hydrocodone pills per month yet fewer HRU and medical costs (all p<0.05). However, during the follow-up period, groups with longer PCD had greater increase in number of inpatient hospitalizations and other types of HRU (length of stay, outpatient hospital visits, office visits, and emergency room visits). The subgroup of patients with PCD <120 days had lower annual all-cause medical costs during follow-up compared with baseline (decreasing $2,624, $2,955, $4,209 per patient per year in Medicaid, Medicare and commercial patients, respectively), while patients with longer PCD during baseline had increased costs (p<0.05). For example, Medicaid patients with 120-179 PCD had an increase of $1,874 and those with ≥180 PCD had an increase of $4,348. These trends were similar for all insurance types. CONCLUSIONS: Extended length of PCD, particularly after 120 days, corresponds with higher patient burden including elevated pill burden and rising HRU and costs in both commercial and public insurance patients with long-term IR hydrocodone use.