Summary: Background: The USA is currently facing a serious opioid misuse epidemic that started with increased prescribing of oxycodone and the inclusion of pain as a fifth vital sign, and eventually resulted in massive overdose mortality. In Europe, including the Netherlands, the medical use of opioids (mainly oxycodone) has also increased since 2009, but an increase in proxies for opioid misuse has not yet been described. Methods: For this retrospective, multi-source database study, data were requested from several national databases in the Netherlands to evaluate the following time trends: (1) number of people with opioid prescriptions, (2) number of hospital admissions related to opioid intoxication, (3) number of people treated for opioid use disorder, and (4) number of people who died from opioid poisoning. Data were presented as the number per 100 000 inhabitants, using population data over the years 2008–17 from Statistics Netherlands (Centraal Bureau voor de Statistiek). Data about the number of people with opioid prescriptions was obtained from the Drug Information Project (Genees- en hulpmiddelen Informatie Project) database hosted by the Dutch National Health Care Institute (Zorginstituut Nederland). Data about opioid-related hospital admissions between 2008 and 2017 were obtained from the Dutch National Hospital Care Basic Registration (Landelijke Basisregistratie Ziekenhuiszorg), a database managed by Dutch Hospital Data. Data about addiction treatment were obtained from the National Alcohol and Drugs Information System (Landelijk Alcohol en Drugs Informatie Systeem). Data on opioid mortality between 2008 and 2017 were obtained from the cause-of-death statistics database hosted by Statistics Netherlands. Each database covered almost the entire population of the Netherlands. Findings: Between 2008 and 2017, the overall number of prescription opioid users nearly doubled from 4109 per 100 000 inhabitants to 7489 per 100 000 inhabitants, mainly because the number of oxycodone users quadrupled from 574 ...