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To investigate and illustrate the use of statistical process control (SPC) for prospective monitoring and detection of regional changes in prescription opioid abuse rates.A demonstration project was conducted by applying several types of SPC charts to Louisiana TANF (Temporary Assistance for Needy Families) applicant self-reported opioid illicit use data collected during 21 months. These charts were constructed and examined for signals of abuse rate changes both at the aggregate statewide level and for each state region (parish) separately.SPC identified increases in opioid illicit use in 2 parishes and subsequent decreases in both regions. These fluctuations were not as apparent when the data were examined using traditional bar graphs and summary tables. The remaining parishes exhibited stable abuse rates with no statistically significant changes over time.These results illustrate proof of concept for monitoring prescription drug abuse regionally via statistical control charts and the potential of this approach for real-time prospective surveillance for abuse rate changes.