Abstract Objective To assess sex differences in disease activity parameters and health-related quality of life in PsA, and to assess whether determinants associated with not reaching treatment target differed between men and women. Methods Routine practice data of 855 PsA patients, who were all tightly monitored and treated, was used. Sex differences including, but not limited to, PsA Disease Activity Score (PASDAS), skin/nail disease, SF-12 PCS/MCS, and inflammatory back pain (IBP) were assessed. Multivariate analyses were used to examine determinants associated with not reaching treatment target (PASDAS ≤ 3.2) in men and women. Results Women had worse scores for—among others—swollen and tender joints, CRP, enthesitis and function (all P < 0.001). Higher PASDAS scores were found for women [3.5 (1.5)] than men [2.7 (1.5), P < 0.001]. Likewise, women were more often not at PASDAS treatment target (OR = 2.03, P < 0.001). No difference in current medication use was found. Nail disease, IBP, number of DMARDs used (past and current), and BMI were associated with not reaching treatment target in the overall sample. For women, but not men, BMI was associated with not reaching PASDAS low disease activity (LDA) (OR between 2.41 and 3.43, P < 0.001). Conclusions Women with PsA in a tightly monitored and treated setting have more severe disease than men. This is demonstrated by worse scores for women in both subjective and objective disease activity measures, in addition to women less often reaching the treatment target. Notably, being overweight is associated with higher disease activity in women, but not men.