The validity of the work productivity and activity impairment (WPAI) questionnaire in the measurement of health-related productivity was demonstrated in gastroesophageal reflux disease and irritable bowel syndrome. The Crohn's disease (CD) specific WPAI (WPAI:CD) was administered in two large clinical trials PRECiSE 1 and PRECiSE 2 that demonstrated the efficacy and tolerability of Certolizumab Pegol subcutaneous once monthly, vs. placebo, in patients with moderate to severe CD. OBJECTIVES: The objective was to compare the WPAI:CD scores of patients categorized by baseline disease severity and health-related quality of life (HRQoL) level, with the a priori assumption that more severe health conditions are associated with higher impairments in work productivity and daily activities. METHODS: The 1330 randomized patients were divided into ‘best' and ‘worst' subgroups determined by the CD Activity Index (CDAI), SF-36, and EQ-5D. ‘Best' health was identified by CDAI scores < median, SF-36 Physical and Mental Component Scores (PCS and MCS) ³ median, and modality ‘1' responses to the EQ-5D dimensions. The non-parametric Wilcoxon test was used to compare the WPAI:CD scores between the subgroups. RESULTS: CD patients with the ‘worst' disease severity (CDAI > 288.1) showed higher impairment in work (+8.9%) and activities (+10.0%) vs. patients with ‘best' health. Similarly patients with ‘worst' HRQoL, as demonstrated by SF-36 PCS < 37.5 and MCS < 37.4, showed higher impairments in work (+20.0% by PCS, +18.5% by MCS) and activities (+22.2% by PCS, +15.5% by MCS) vs. ‘best' HRQoL. Patients with the ‘worst' EQ-5D states reported more impairment in work (+15.2% averaged over the 5 dimensions) and activities (+17.3%) vs. patients with the ‘best' states. All p-values were <0.001. CONCLUSION: The measurement of expected differences in work and activity impairment by disease severity and HRQoL levels supports the discriminant validity of the WPAI:CD.