Objective The aim of this multi-center study was to assess predictive factors for work-day loss as an indirect cost element in Behcet's syndrome (BS). Methods In this cross-sectional, multi-center study, 834 BS patients (F/M: 441/393, age mean: 38.4 +/- 10.9 years) were included. Data were collected by a questionnaire regarding treatment protocols, disease duration, smoking pattern, frequency of medical visits during the previous year and self-reported work-day loss during the previous year. Results Work-day loss was observed in 16.2% of patients (M/F: 103/32). The percentages of being a smoker (81.8%), using immunosuppressive (IS) medications (82%), and having disease duration <5 years (74%) were higher in male patients with work-day loss (P < .05). The majority of males (90.9%) had more than four clinic visits during the previous year. Moreover, the mean work-day loss (30.8 +/- 57.7 days) was higher in patients with vascular involvement (56.1 +/- 85.9) than those without (26.4 +/- 50.6 days) (P = .046). In addition, increased frequency of ocular involvement (25.9%) was also observed in patients with work-day loss compared to others (8.6%) (P = .059). Conclusion Work-day loss was associated with both vascular and ocular involvement. Close associations were observed among male gender, early period of the disease, frequent medical visits, being a smoker and treatment with IS medications in patients with work-day loss.