Abstract Rationale Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid‐related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. Aims and Objectives This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. Methods In a cross‐sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM‐5 criteria. Independent T ‐tests, Pearson χ 2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. Results A total of 997 patients were screened, of which 15% ( n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% ( n = 21) showed signs of prescription opioid misuse, and 9.8% ( n = 9, 95% CI: 4.5–17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. Conclusion This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid‐related problems.