OBJECTIVES:  To quantify the impact of etanercept (ETN) on work and activity impairment in employed patients with moderate to severe rheumatoid arthritis (RA) in US community practices.  METHODS:  In this prospective, observational study, 55 sites across the US enrolled employed, TNF-naïve, moderate to severe RA patients who initiated 50 mg/week ETN between January 1, 2009 and March 5, 2010.  Telephone interviews were conducted at baseline (prior to or at the time of their first ETN dose) and 6 months (after the start of ETN), collecting patient demographic and clinical information, in addition to evaluating work and activity impairment using the Work Productivity and Activity Impairment Questionnaire (WPAI).  The change in WPAI outcomes after 6 months was assessed through a Wilcoxon signed rank test on all enrolled patients. RESULTS:  At baseline, 204 enrolled patients (mean age, 46.6 years (SD: 10.9); 72.6% female, 83.8% in full-time employment; mean duration of RA, 5.2 years) reported that the overall work impairment, work absenteeism, work presenteeism (reduction in productivity at work) and total activity impairment due to RA were 43.2%, 9.9%, 39.7% and 56.1%, respectively.  All four WPAI outcomes improved after initiation of ETN therapy.  At 6 months, 153 patients remained on therapy and the overall respective WPAI scores demonstrated a mean percent improvement from baseline of 28.7% (p<0.0001), 54.6% (p=0.0009), 33.2% (p<0.0001) and 37.3% (p<0.0001).  In addition, mean hours lost from work over the last 7 days because of RA decreased from 3.8 hours at baseline to 1.6 hours at 6 months (62.5% decrease in hours lost; p=0.0005).  CONCLUSIONS:  In working patients with moderate to severe RA, ETN had a significant impact on reducing overall work impairment, absenteeism, presenteeism, and activity impairment.  Data demonstrate the positive impact of ETN on the ability to work and perform regular activities when used under real world conditions.