Patterns of psoriasis characteristics by sex are not fully understood. Evaluate patient characteristics by sex at enrollment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Two PSOLAR cohorts were evaluated by sex: patients who were biologic-naïve (n = 3329) and patients who were systemic therapy-naïve (n = 1290) at entry. Baseline demographic and disease characteristics, medical history, social activity, and lifestyle risk factors were collected for all patients and were compared between males and females using an independent samples t-test for continuous variables and chi-square tests for categorical variables. In both cohorts, disease duration was similar for males and females; however, disease severity based on baseline Physician Global Assessment and body surface area of psoriasis was greater in males versus females ( < .05). Baseline Dermatology Life Quality Index scores were higher for biologic-naïve females than for males ( = .008). In both cohorts, females were significantly more likely than males to have a history of anxiety, depression, and cancer excluding nonmelanoma skin cancer, to have received systemic steroid therapy, and to have health insurance; males were significantly more likely than females to have a history of cardiovascular disease, smoking, and alcohol consumption, and to work full time. Based on patient data obtained at entry into PSOLAR, significant differences in psoriasis disease characteristics, and medical, family, and social history-related variables were observed between males and females. Among systemic therapy-naïve patients, there was a greater negative impact on quality of life for females compared with males, despite generally lower objective disease severity for females.