Objectives: To assess the relationship between disease activity and work ability, quality of life (QoL), and fatigue in patients with RA during a 12-month course of the tumour necrosis factor (TNF)-blocking agent adalimumab. Methods: RA patients in the working age category who started treatment with adalimumab were included consecutively and followed up for 12 months. Generalized estimating equation (GEE) analyses were used to study relationships between disease activity and the outcome variables work ability, QoL, and fatigue at baseline, 6 months, and 12 months. Disease activity was measured using the 28-joint Disease Activity Score (DAS28), quality of life was assessed with the Rheumatoid Arthritis-specific Quality of Life instrument (RAQoL), and fatigue was assessed using the Checklist Individual Strength (CIS) questionnaire and the Need for Recovery scale (NFR). Results: After 1 year, markedly improvement was seen not only in the DAS28 (from 5.2 ± 1.2 to 3.1 ± 1.6) but also in work ability, RAQoL, and work-related fatigue, which improved by 50, 29, and 34%, respectively. At all three time points strong significant associations were observed between DAS28 and work ability, RAQoL, and work-related fatigue and this relationship remained strong after adjustment for confounders. Conclusions: Disease activity was associated with QoL, work-related fatigue, and work ability in a group of RA patients treated with adalimumab for 1 year. As improvement in these factors influences work participation positively and work ability measures more than health status, the current results suggest that simple tools such as work ability should be used more frequently as outcome measures in trials with RA patients. © 2010 Informa UK Ltd.