The opioid epidemic is a well-recognized national patient safety issue. High-risk opioid prescribing can contribute to misuse. Provider prescribing has come under increased scrutiny and several states have implemented prescription drug monitoring programs (PDMPs). Prior research suggests that such programs have the potential to reduce opioid-related harm. This study used commercial claims data to assess the impact of PDMPs implemented in four states in 2012–2013 on opioid prescribing. By the end of 2014, all four states with PDMPs demonstrated a greater reduction in the average amount of morphine-equivalents prescribed per person per quarter compared with states without these programs. One state demonstrated a decrease in the percentage of people who filled an opioid prescription. The authors conclude that PDMPs have the potential to reduce opioid use and improve prescribing practices. An Annual Perspective highlighted safety issues associated with opioid medications.