OBJECTIVES: Irritable bowel syndrome with constipation (IBS-C) can decrease work productivity and increase activity impairment, resulting in a substantial economic burden for patients and employers. Linaclotide, a minimally-absorbed guanylate cyclase C agonist (GCCA), significantly improved abdominal and bowel symptoms in 2 Phase 3 IBS-C trials. We evaluated the linaclotide treatment effect on work productivity and activity impairment in IBS-C patients. METHODS: In 2 Phase 3 trials, 1602 adults with IBS-C (modified Rome II criteria) were randomized to oral linaclotide 290 μg once daily or placebo. The self-administered 6-item Work Productivity and Activity Impairment questionnaire for IBS-C (WPAI:IBS-C) was used to evaluate IBS-C symptom-related absenteeism (work hours missed), presenteeism (degree symptoms affected work productivity), overall work productivity loss (absenteeism+presenteeism) and daily activity impairment (degree symptoms affected activities) over the previous week. Using pooled intent-to-treat data, changes in WPAI:IBS-C scores from baseline to Weeks 4, 8, and 12 were assessed by analysis of covariance and represented as percentages (higher percentage=greater productivity loss and activity impairment). Absenteeism, presenteeism and work productivity assessments included employed patients only. RESULTS: Compared to placebo, linaclotide significantly reduced presenteeism, overall work productivity loss and daily activity impairment, and numerically decreased absenteeism, at Weeks 4, 8 and 12. Mean changes from baseline to Week-12 for linaclotide and placebo, and the corresponding treatment effect (LS-means difference between linaclotide and placebo, shown as “Δ”), respectively, were: presenteeism, ‑18.4% and ‑13.1% (Δ=-5.2, P<0.0001); overall work productivity loss, ‑19.4% and ‑13.0% (Δ=-6.1, P<0.0001); daily activity impairment, ‑19.9% and ‑15.2%(Δ=-4.7, P<0.0001); absenteeism, ‑1.6% and ‑0.9% (Δ=-0.5, P=0.311). Assuming a 40-hour work week, linaclotide reduced overall work productivity loss by 1.6-2.4 hours/week. CONCLUSIONS: Linaclotide significantly reduced presenteeism, overall work productivity loss and daily activity impairment for IBS-C patients versus placebo. Significant improvements were evident at Week-4 and maintained through Week-12.