IMPORTANCE: There are increasing options for systemic combination therapy for psoriasis but a lack of literature around the characteristics of patients who are started on these regimens. OBJECTIVE: We aimed to determine how combination systemic therapy patients differ from monotherapy patients in their social, medical, or treatment history. DESIGN: This was a cross-sectional study of patients enrolled in the Corrona Psoriasis Registry. Descriptive characteristics were compared in biologic monotherapy and combination therapy groups. SETTING: The Corrona PsO registry is a prospective multicenter observational disease-based registry with patients recruited from 154 private and academic practice sites in the US and Canada with 373 participating dermatologists. PARTICIPANTS: Patients 18 years of age or older who enrolled in the Corrona Psoriasis Registry between April 2015 and March 2017 and initiated an eligible biologic therapy at the time of enrollment were included. EXPOSURES: Eligible biologic therapies included adalimumab, etanercept, infliximab, ixekizumab, secukinumab, and ustekinumab. Non-biologic and small molecule adjunctive therapies included acitretin, apremilast, CsA, and MTX. RESULTS: Patients on combination therapy were more likely to identify as black, to have Medicaid, and to report disabled work status. While combination therapy patients were more likely to have concomitant PsA, no major differences were seen in disease morphology, duration, IGA, PASI, or BSA affected at treatment initiation. CONCLUSIONS: Various demographic and socioeconomic factors are associated with use of combination systemic therapy compared to use of systemic monotherapy for psoriasis. An association with commonly used disease severity indices was not observed. RELEVANCE: An understanding of which patients are more likely to be prescribed combination systemic therapy will provide important context for long-term efficacy and safety data as they become available.