OBJECTIVES: The federal government provided approximately $29 million from 2003–2007 to help states establish and maintain prescription drug monitoring programs (PDMPs) aimed at reducing diversion and abuse of pharmaceuticals.  The objective of this study is to compare aggregated prescription drug-related mortality rates in states with active PDMPs compared to states with inactive PDMPs. METHODS: Data on ten states with prescription drug-related mortality rates are available from the Drug Abuse Warning Network (DAWN).  As of 2007, 6 states had active PDMPs: Maine, Massachusetts, New Mexico, Oklahoma, Utah and Virginia.  Whereas four states had inactive PDMPs: Maryland, New Hampshire, Oregon and Vermont.  Independent samples t-test was used to determine significance (p=0.10) in mean mortality rates between active and inactive PDMPs.  RESULTS: Among the 10 states, 4454 drug-related deaths were reported in 2007.  States with active PDMPs received a mean of $908,756 compared to $287,056 for states with inactive PDMPs.  Among states with active PDMPs, New Mexico had the highest drug-related mortality rate (21.0%) and among states with inactive PDMPs, Maryland had the highest mortality rate (14.6%).  A t-test showed no significant difference (p=0.37) in mean ± SD drug-related death rate per 100,000 people associated with active PDMPs (14.2±5.4) compared to states with inactive PDMPs (11.9±2.2).    CONCLUSIONS: Drug-related mortality rates were lower in states with inactive programs, when compared to states with active PDMPs.  This result may be representative of political pressure to enact programs in states with higher mortality rates.  Although the sample size represents 20% of states, results should be viewed with caution.  PDMPs are designed to decrease diversion and abuse, as well as associated morbidity and mortality; however more research is needed to determine their effectiveness and to devise ways to maximize their utility.