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BACKGROUND Since early 2016, an increasing number of states passed legislations that limit the duration and/or dosage of initial opioid prescriptions or opioids for acute pain. OBJECTIVE The objective of this study was to assess changes in the number of opioid prescriptions covered by Medicaid and received by Medicaid patients associated with state implementation of legislative limits on initial opioid prescriptions. RESEARCH DESIGN We explored the natural experiment resulting from the staggered implementation of state legislative limits. The analysis adopted a Difference-in-Differences framework and controlled for other major state policies bearing implications for prescription opioid use. The main analysis included 26 states that implemented limits from early 2016 to late 2018. A secondary analysis included all 50 states and the District of Columbia. MEASURES Population-adjusted state-quarter level counts of Schedule II and III opioid prescriptions received by Medicaid patients, based on data from the Medicaid State Drug Utilization Data and state Medicaid enrollment reports for 2013-2018. RESULTS Implementation of legislative limits on initial opioid prescriptions was associated with a 7% reduction in the number of opioid prescriptions per 100 Medicaid enrollees. Such reduction was largely attributable to a reduction in Schedule II opioid prescriptions. Secondary analysis by including all jurisdictions and sensitivity checks supported the robustness of results. CONCLUSION The recent implementation of state legislative limits on initial opioid prescriptions was associated with meaningful reductions in the volume of Schedule II opioid prescriptions received by Medicaid patients.