OBJECTIVE: To explore the effect of health-related and contextual factors on presenteeism, absenteeism, and overall work productivity loss in patients with active ankylosing spondylitis (AS). METHODS: Consecutive patients with AS starting their first tumor necrosis factor inhibitor and in paid employment were eligible. Patients completed the Work Productivity and Activity Impairment (WPAI) questionnaire for AS to assess presenteeism, absenteeism, and overall work productivity loss in the previous 7 days. In addition, they answered questions about work characteristics (type, characteristics of workplace, satisfaction of contacts with colleagues, and importance of work in life) and health status [Bath AS Functional Index (BASFI), AS Disease Activity Score-C-reactive protein (ASDAS-CRP)]. Physicians assessed the Bath Ankylosing Spondylitis Metrology Index, presence of articular and extraarticular manifestations, comorbidities, and laboratory indicators of inflammation. Stepwise regression models were computed to determine which work-related and health-related factors contributed to WPAI outcomes. RESULTS: The study included 80 patients. The WPAI presenteeism, absenteeism, and overall work productivity loss scores were 49.1%, 30.2%, and 53.1%, respectively. Presenteeism was associated with higher BASFI, female sex, and poor quality of contact with colleagues. Absenteeism was associated with increasing age, current smoking status, higher ASDAS-CRP, and low importance of work for life. Overall work productivity loss was associated with female sex, higher BASFI, past adaptation of job because of illness, number of working hours, and manual profession. CONCLUSION: Both health-related and contextual factors contribute to work limitations in patients with AS and suggest additional opportunities for improvement by addressing the working environment.