Background: Patterns of psoriasis characteristics by gender are not fully understood. Objective: Evaluate patient characteristics by gender at enrollment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: Two PSOLAR cohorts were evaluated by gender: 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. Results: 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 (P < .05). Baseline Dermatology Life Quality Index scores were higher for biologic-naïve females than for males (P = .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. Conclusions: 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.