ABSTRACT: Pain management clinic (PMC) laws were enacted by 12 states to promote appropriate opioid prescribing, but their impact is inadequately understood. We analyzed county-level opioid overdose deaths (National Vital Statistics System) and patients filling long-duration (≥30 day) or high-dose (≥90 morphine milligram equivalents per day) opioid prescriptions (IQVIA, Inc.) in the United States in 2010-2018. We fitted Besag-York-Mollié spatiotemporal models to estimate annual relative rates (RRs) of overdose and prevalence ratios (PRs) of high-risk prescribing associated with any PMC law and 3 provisions: payment restrictions, site inspections, and criminal penalties. Laws with criminal penalties were significantly associated with reduced PRs of long-duration and high-dose opioid prescriptions (adjusted PR = 0.82, 95% credible interval (CrI): 0.82, 0.82, and adjusted PR = 0.73, 95% CI: 0.73, 0.74 respectively) and reduced RRs of total and natural/semisynthetic opioid overdoses (adjusted RR = 0.86, 95% CrI: 0.80, 0.92, and adjusted RR = 0.84, and 95% CrI: 0.77, 0.92, respectively). Conversely, PMC laws were associated with increased relative rates of synthetic opioid and heroin overdose deaths, especially criminal penalties (adjusted RR = 1.83, 95% CrI: 1.59, 2.11, and adjusted RR = 2.59, 95% CrI: 2.22, 3.02, respectively). Findings suggest that laws with criminal penalties were associated with intended reductions in high-risk opioid prescribing and some opioid overdoses but raise concerns regarding unintended consequences on heroin/synthetic overdoses.