OBJECTIVES:  Patients, healthcare providers, policymakers, and payers are intent on finding solutions to the opioid epidemic in the US. One solution enacted by the Drug Enforcement Administration in 2014 was to reschedule hydrocodone combination products (HCPs) from C-III to C-II. This change was aimed at restricting the availability of the most commonly prescribed prescription in the US. The objective of this study was to assess the immediate change in opioid utilization at the time of rescheduling, focusing on the substitution of HCPs with acetaminophen/codeine (APAP/codeine, C-III) and tramadol (C-IV), using prescription monitoring program (PMP) data. METHODS:  An interrupted time-series design was used with data from the Texas PMP spanning June 1, 2013 to April 8, 2015. The PMP captures all controlled substance prescriptions (C-II – CV) dispensed from outpatient pharmacies. An interrupted time series design was employed to address the study objective. Opioids were grouped into four categories: 1) HCPs; 2) other C-II opioids; 3) APAP/codeine; and 4) tramadol. Each prescription was converted to daily morphine milligram equivalents (MMEs) per 100 population for analysis. RESULTS:  The total number of prescription opioids dispensed was 30,745,113. Most were for HCPs (67.4%), followed by all other C-II opioids (12.1%), APAP/codeine (10.1%), and tramadol (10.4%). At the time of rescheduling, the mean utilization of opioids (in daily MMEs per 100 population) decreased from 67.4 to 45.2 (-32.9%) for HCPs, increased from 1.4 to 5.0 (271.5%) for APAP/codeine, and increased from 3.1 to 11.0 (256.2%) for tramadol. After rescheduling, the rate of change of APAP/codeine utilization increased by 0.06 daily MMEs per 100 population per day. CONCLUSIONS:  Rescheduling resulted in increased use of APAP/codeine and tramadol. HCP use was restricted, as intended. The unintended consequences of increased heroin usage and potential negative impacts to patients’ quality of life should also inform future policy.