Opioid medications carry high risk for adverse drug events, and increases in opioid abuse have led to an epidemic of overdose deaths. State-level prescription drug monitoring programs are intended to identify high-risk prescribing and patient behaviors associated with opioids. This study used secondary data sources to determine whether implementing a drug monitoring program decreased opioid overdose deaths compared to the pre-implementation period. States with more complete and timely opioid monitoring achieved greater overdose reductions compared to states with less comprehensive programs. These results clearly support universal implementation and strengthening of state prescription drug monitoring programs. A WebM&M commentary discussed a death due to an opioid overdose.