Background: Rheumatoid arthritis (RA) and other rheumatic conditions not only fundamentally affect patients' quality of life and physiological needs but are also negatively associated with work ability. The costs of poor work ability, which, in sum, are more than treatment costs, pose an economic burden to society and patients. Work ability in RA appears to be multifactorial; symptoms such as pain, swelling, and stiffness play a major role, as these directly affect functional disability. Also, RA patients typically suffer from reduced muscle strength. Lower extremity function and grip strengths especially impair their quality of life. However, the role of muscle strength and disease activity as determinants of work ability have not yet been studied. Objective: The primary objective of this study is to compare work ability in working-age participants with seropositive RA and with high and low disease activity; the secondary objective is to evaluate the association of muscle strength, functional ability, and frailty with work ability. Methods: This monocentric cross-sectional study will be conducted at a rheumatologic outpatient clinic and day hospital with approximately 100 seropositive RA patients aged <65 years. A clinical disease activity index as a measure for rheumatoid disease activity will be assessed during the patients' routine visits at the clinic. Work ability, frailty, and functional disability will be evaluated with (self-reported) questionnaires as well as with physical tests (Work Ability Index/Score; Health Assessment Questionnaire Disability Index; Survey of Health, Ageing, and Retirement in Europe Frailty Instrument; Short Physical Performance Battery). Muscle strength will be determined with dynamometer measurements of isometric hand grip strength and quadriceps femoris muscle contraction strength. Sleep quality (Medical Outcomes Study Sleep Scale) and sexual functioning as physiological needs will additionally be determined with self-reported questionnaires. Results: For this study funding has already been awarded and enrollment has been completed. Data are currently being evaluated. Conclusions: This study will evaluate the association of work ability with modifiable parameters such as muscle strength and functional ability. It will provide further insights into work ability in RA and its associated risk factors. Any evidence of association will motivate further research, and the findings might encourage interventions focused specifically on improving muscle strength and lower extremity function to positively affect work ability.