Objectives To determine (1) pharmacists’ perceptions of how rescheduling of hydrocodone combination products (HCPs) from Drug Enforcement Agency (DEA) Schedule III to DEA Schedule II has influenced prescription volume and revenue, pharmacy workflow management, and patient outcomes; and (2) whether perceptions differed between pharmacists who support versus those who oppose HCP rescheduling. Design A cross-sectional mail survey. Setting Texas community pharmacies from October to December 2015. Participants One thousand randomly selected, registered Texas community pharmacists drawn from the Texas State Board of Pharmacy registry. Main outcome measures Pharmacists’ perceptions, measured on a 5-point Likert scale of HCP rescheduling and its impact on prescription volume and revenue, workflow management, and patient outcomes. Measures were developed specifically for this study. Results The response rate was 17% (n = 164). The majority of pharmacists (70.4%) supported HCP rescheduling. More than 80% of respondents perceived that the volume of 2 alternative pain medications—tramadol (DEA Schedule IV) and acetaminophen with codeine (DEA Schedule III) prescriptions dispensed—either “increased” or “significantly increased” (82.0% and 85.8%, respectively) following rescheduling. Overall, pharmacists who opposed rescheduling were significantly more likely to report negative perceptions regarding revenue (P = 0.0142), inventory management (P = 0.0024), and drug shortages (P = 0.0005) than those who supported rescheduling. However, pharmacists who supported rescheduling had more positive perceptions about electronic prescribing (P <0.0115), patient safety (P <0.001), drug abuse (P <0.0001), and legitimate use (P <0.0001). Conclusion Results showed that legislative efforts, such as rescheduling HCPs, influenced pharmacists’ perceptions of practice and patient outcomes. Currently, little is known regarding the impact of HCP rescheduling on pharmacy practice. As new laws are passed to address the opioid epidemic in America, more research will be needed to determine whether legislation is an effective means for managing appropriate access to HCPs and other narcotic analgesics.