OBJECTIVES: Hydrocodone combination products (HCPs) were the most prescribed drugs in the US in 2012. HCPs were rescheduled from C-III to C-II beginning October 6, 2014. Physicians and pharmacists have expressed concerns about the impact rescheduling could have on patient care. Additionally, Texas and Louisiana have many differences in prescribing regulations which may impact patient care, specifically regarding C-II prescribing. The objective of this study was to assess the impact of rescheduling HCPs on the utilization of opioid pain relievers (OPRs) in Texas and Louisiana. METHODS: A retrospective cohort design was employed using data from the Texas and Louisiana prescription drug monitoring programs (PDMPs), consisting of prescription level information for all C-II to C-V drugs dispensed from community pharmacy settings from June 1, 2013 to April 8, 2015. Interrupted time-series analysis was conducted on total OPR volume (i.e., morphine milligram equivalents) dispensed on a weekly basis within four categories: HCPs, C-II OPRs, acetaminophen with codeine, and tramadol by state. RESULTS: The final cohort contained 38,163,347 OPR prescriptions in Texas and Louisiana, of which 78.9% were from Texas.  Volume of HCPs declined 955 mg/week (-45.1%, p<0.05) in Texas and declined 132 mg/week (-23.7%, p<0.05) in Louisiana post-rescheduling. Volume of C-II OPRs increased 20,007 mg/week (75.4%, p<0.05) in Texas and increased 10,523 mg/week (6.0%, p<0.05) in Louisiana post-rescheduling. Acetaminophen with codeine volume increased 58,539 mg/week (62.2%, p<0.05) in Texas and increased 3,889 mg/week (8.6%, p<0.05) in Louisiana post-rescheduling. Volume for tramadol increased 757,322 mg/week (1,073.3%, p<0.05) in Texas and remained unchanged (-1.5%, p=0.68) in Louisiana post-rescheduling. CONCLUSIONS: Rescheduling HCPs resulted in decreased volume of HCPs, increased volume of C-II OPRs, increased volume of acetaminophen with codeine, and increased volume of tramadol in Texas (up to levels comparable to Louisiana). Pain management using OPRs changed significantly due to rescheduling within these two states.