Opioids are known to be high-risk medications, and their misuse is an increasingly recognized patient safety problem. This data analysis from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project delineates trends in opioid-related hospitalizations by state between 2005 and 2014. Both hospital stays and emergency department visits related to opioids have been increasing every year, paralleling trends in opioid overdose deaths. There was substantial variation across states, and the overall rate of opioid-related inpatient stays was 225 per 100,000 population for 2014. These data underscore the need to improve the safety of opioid use to prevent morbidity and mortality.