AbstractDespite the significant cost of prescription (Rx) drug abuse and calls from policymakers for effective interventions, there is limited research on the effects of policies intended to limit such abuse. This study estimates the effects of prescription drug monitoring (PDMP) programs, which constitute a key policy targeting access to non‐medical use of Rx drugs. Based on objective indicators of abuse as measured by substance abuse treatment admissions and mortality related to Rx drugs, estimates do not suggest any substantial effects of instituting an operational PDMP. We find, however, that mandatory‐access provisions, which raised PDMP utilization rates by actually requiring providers to query the PDMP prior to prescribing a controlled drug, are significantly associated with a reduction in Rx drug abuse. The effects are driven primarily by a reduction in opioid abuse, generally strongest among young adults (ages 18 to 24), and underscore important dynamics in the policy response. Robustness checks are consistent with a causal interpretation of these effects. We also assess potential spillovers of mandatory PDMPs on the use of other illicit drugs and find a complementary reduction in admissions related to cocaine and marijuana abuse.