Abstract Purpose Problematic substance use and Substance Use Disorders (SUD) are common in all layers of the population. Several studies suggest higher prevalence rates of problematic substance use among physicians compared to the general population, which is harmful for themselves and potentially impairs quality of care. However, nationwide comparison with a highly educated reference group is lacking. Using nationwide register data, this study compared the prevalence of clinical SUD diagnoses and alcohol consumption patterns between physicians and a highly educated reference population. Methods A retrospective study was performed using registry data from 2011 up to and including 2019, provided by Statistics Netherlands. From the data, a highly educated reference group was selected and those with an active medical doctor registration were identified as “physicians”. Clinical SUD diagnoses were identified by DSM-IV codes in mental healthcare registries. Benchmark analyses were performed, without statistical testing, to compare the prevalence of SUD diagnoses and alcohol consumption patterns between physicians and the reference population. Results Clinical SUD diagnoses were found among 0.3% of the physicians and 0.5% of the reference population, with higher proportions of sedative use disorder among physician patients. Among drinkers, the prevalence rates of heavy and excessive drinking were respectively 4.0% and 4.3% for physicians and 7.7% and 6.4% for the reference population. Conclusion Prevalence rates of SUD diagnoses were fairly comparable between physicians and the highly educated reference population, but physicians displayed more favorable alcohol consumption patterns. The use of sedatives by physicians might deserve attention, given the relatively higher prevalence of sedative use disorder among physicians. Overall, we observed relatively low prevalence rates of SUD diagnoses and problematic alcohol use, which may reflect a treatment gap and social desirable answers.