Abstract Objectives To evaluate the prevalence, magnitude and potential determinants of work productivity impairment in patients with Behçet’s syndrome (BS), focusing on the role of irreversible organ damage. Methods A post hoc analysis of the BS Overall Damage Index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI:GH outcomes was evaluated by regression analysis. Results Of 148 patients, 34.5% were unemployed, with age [odds ratio (OR) 1.035] and BODI score (OR 1.313 for a 1-unit increase) as the only factors significantly (P < 0.05) associated with the unemployment state. Overall work impairment was reported in ≈64.2% of the employed patients. Indeed, 22.7% reported missing work hours due to their health (absenteeism), with a mean time loss of 34.4%, whereas 60.2% declared reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (β = 0.225); female sex (β = 0.260), physician global assessment of disease activity (β = 0.502) and an increased BODI score (β = 0.166 for 1-point increase) with presenteeism; and fibromyalgia (β = 0.246), Physician Global Assessment (β = 0.469) and musculoskeletal damage (β = 0.325) with overall work impairment. Conclusions Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.