Purpose To examine men and women’s perceptions of inter-role balance/imbalance in work, arthritis, and personal roles and its association with demographic, health and employment factors, including job stress, career satisfaction, job disruptions, absenteeism and perceived productivity losses. Methods Participants were employed, aged ≥40 years and diagnosed with osteoarthritis or inflammatory arthritis. They were recruited through community advertising and rheumatology clinics in two Canadian provinces. Respondents completed a 35–45 min telephone interview and a 20-min self-administered questionnaire assessing role perceptions [(arthritis negatively impacts work (A → W); work/personal life negatively impact arthritis (W/P → A); work as a positive role (W +))], demographic, health and work context information. Analyses included exploratory factor analysis and multivariate regressions. Results Findings revealed similarities between men (n = 104) and women (n = 248) in health, work and role perceptions, although women reported more benefits of working with arthritis (W+) than men. Some gender differences were found in factors associated with inter-role perceptions highlighting the importance of children, fatigue, unpredictable work hours, job control, and workplace activity limitations. Role perceptions were associated with work outcomes but only one perception, W/P → A, interacted with gender. Among men, greater perceptions that work and personal demands interfered with managing arthritis were associated with more job disruptions. Conclusions This study revealed negative and positive inter-role perceptions related to working with a chronic illness and associations with work outcomes. It highlights potentially modifiable factors that could assess risk and inform interventions to improve role balance and working experiences.