AbstractAimTo quantify the healthcare costs associated with opioid use disorder among members in a public healthcare system and compare them with healthcare costs in the general population.DesignRetrospective cohort study.SettingInpatient and outpatient care settings of Israel's largest public healthcare provider (that covers 4.7 million members).ParticipantsParticipants included 1173 members who had a diagnosis of opioid use disorder in the years between 2013 and 2018. Each patient was matched with 10 controls based on age and sex.MeasurementsThe main outcome was monthly healthcare costs.FindingsThe mean monthly healthcare cost of members with opioid use disorder was $1102 compared with $211 among controls (5.2‐fold difference; 95% CI, 4.6–6.0). After excluding members with heroin related diagnoses before the index date (to focus on prescription opioids), this healthcare cost ratio did not substantially change (4.6‐fold; 95% CI, 3.9–5.4). Members with opioid use disorder under the age of 65 years had a cost difference of 6.1‐fold (95% CI, 5.2–7.1), whereas those 65 years and older experienced cost difference of 3.4‐fold (95% CI, 2.6–4.5), compared with controls. The category with the highest cost for members with opioid use disorder was inpatient services, which was 8.7‐fold (95%CI, 7.2–10.4) greater than among controls.ConclusionsHealthcare costs among individuals with opioid use disorder in Israel's public health system are substantially higher than among controls, at least partially attributable to prescription opioid use disorder. Differences are greater among individuals under 65 years.