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Abstract In 2016, more than 11 million Americans abused prescription opioids. The National Institute on Drug Abuse considers the opioid crisis a national addiction epidemic, as an increasing number of people are affected each year. Using the framework developed in mathematical modelling of infectious diseases, we create and analyse a compartmental opioid-abuse model consisting of a system of ordinary differential equations. Since $$40\%$$ of opioid overdoses are caused by prescription opioids, our model includes prescription compartments for the four most commonly prescribed opioids, as well as for the susceptible, addicted and recovered populations. While existing research has focused on drug abuse models in general and opioid models with one prescription compartment, no previous work has been done comparing the roles that the most commonly prescribed opioids have had on the crisis. By combining data from the Substance Abuse and Mental Health Services Administration (which tracked the proportion of people who used or misused one of the four individual opioids) with data from the Centers of Disease Control and Prevention (which counted the total number of prescriptions), we estimate prescription rates and probabilities of addiction for the four most commonly prescribed opioids. Additionally, we perform a sensitivity analysis and reallocate prescriptions to determine which opioid has the largest impact on the epidemic. Our results indicate that oxycodone prescriptions are both the most likely to lead to addiction and have the largest impact on the size of the epidemic, while hydrocodone prescriptions had the smallest impact.