BackgroundPityriasis versicolor (PV), a cutaneous fungal infection, most commonly affects adolescents and young adults and is associated with hyperhidrosis and humid weather. Understanding other factors associated with PV might help improve diagnostic and treatment practices.ObjectivesPV's associations with patient demographics, comorbidities and medication exposures were assessed using the All of Us Database, a large, diverse, national database from the United States.MethodsA case–control study with multivariable analysis was performed.ResultsWe identified 456 PV case‐patients and 1368 control‐patients. PV case‐patients (vs. control‐patients) were younger (median age [years] (standard deviation): 48.7 (15.4) vs. 61.9 (15.5); OR: 0.95, CI: 0.94–0.96) and more likely to be men versus women (42.8% vs. 33.9%, OR: 1.45, CI: 1.16–1.79) and Black (19.5% vs. 15.8%, OR: 1.35, 95% CI: 1.02–1.80) or Asian (4.6% vs. 2.7%, OR: 1.86, CI: 1.07–3.24) versus White. PV case‐patients more frequently had acne (5.3% vs. ≤1.5%, OR: 5.37, CI: 2.76–10.48) and less frequently had type 2 diabetes mellitus (T2DM) (14.7% vs. 24.7%, OR: 0.52, CI: 0.39–0.70) and hypothyroidism (OR: 10.3% vs. 16.4%, OR: 0.59, CI: 0.42–0.82). In multivariable analysis, PV odds were significantly higher in those with acne and lower in those with T2DM, older age and female sex.ConclusionsOur results may be used as a basis for future studies evaluating whether acne treatment may decrease PV risk. Physicians could educate patients with acne about PV, including strategies to control modifiable PV risk factors, such as avoidance of hot and humid environments and avoidance of use of topical skin oils.