OBJECTIVES:   To assess work productivity loss among multiple sclerosis (MS) patients and the resulting indirect social cost due to MS from a real-world observational study. METHODS:   ROBUST is a 12-month, US prospective, observational, open-label, single-arm, multi-center outcomes study of Interferon β-1b given every other day for relapsing forms of MS.  For this analysis, baseline data from the Work Productivity and Activity Impairment questionnaire specific for MS (WPAI) were used.  Productivity outcomes including absenteeism (work time missed), presenteeism (reduced on-the-job effectiveness) and overall work productivity loss were calculated from WPAI.  Indirect social cost was estimated by modeling US national average wage data by education level from the Bureau of Labor Statistics to the WPAI scores.  Work productivity and indirect social cost were compared across patient sociodemographic characteristics and disease severity.  RESULTS:   A total of 191 MS patients were evaluated at baseline with 114 working either full-time (78.1%) or part-time (21.9%).  In this working sample, 75.4% were females, 72.8% were married, 71.1% were below 50 years old and a majority were White (88.5%).  The overall productivity loss due to MS among full-time employed patients and part-time employed patients was 42.5% (SD: 26.9) and 42.1% (SD: 30.6), respectively.  This translates into a substantial productivity loss of 17 hours of loss time in a 40-hour work-week for full-time workers and 8.4 hours of loss time in a 20-hour work week for part-time workers.  At average wages, this productivity loss equates to an indirect annual social loss of $18,106 per patient (SD: $13,265) among full-time workers and $8,871 per patient (SD: $7,080) among part-time workers.  Indirect social costs were significantly correlated with increasing MS severity (r=0.21; p=0.0.029).  CONCLUSIONS:   Multiple sclerosis results in a substantial loss of work productivity among patients, which collectively results in significant indirect social cost.  The MS-related indirect social costs increase with increasing MS severity.