Purpose: This study presented the construct of Work–Health Balance (WHB) and the design and validation of the Work–Health Balance Questionnaire (WHBq). More and more workers have a long-standing health problem or disability (LSHPD). The management of health needs and work demands is crucial for the quality of working life and work retention of these workers. However, no instrument exists measuring this process. The WHBq assesses key factors in the process of adjusting between health needs and work demands. Method: We tested the reliability and validity of 38 items with cross-sectional data from a sample of 321 Italian workers (mean age = 45 ± 11 years) using exploratory factor analysis (EFA), Rasch analyses, and the correlations with other relevant variables. Results: The instrument ultimately consisted of 17 items that reliably measured three factors: work–health incompatibility, health climate, and external support. These dimensions were associated with well-being in the workplace, dysfunctional behaviors at work, and general psychological health. A higher level on the WHB index was associated with lower levels of presenteeism, emotional exhaustion, workaholism, and psychological distress and with higher levels of job satisfaction and work engagement, supporting the construct validity of the instrument. Conclusion: The WHBq shows good psychometric characteristics and strong and theoretically consistent relationships with important and well-known variables. These results make the WHBq a promising tool in the study and management of health of employees, especially for the work continuation of employees returning to work with LSHPD.