Purpose: To translate and cross-culturally adapt, the Work Role Functioning Questionnaire 2.0 to Persian (WRFQ-Pr), and evaluate reliability and validity. Material and Methods: Standardized protocols were followed including forward-backward translation then synthesis/consolidation. Subsequent pilot investigation of the draft WRFQ-Pr (n = 50, male = 68%, age = 33.5 ± 7.3 years) tested the alternative wording and determined face and content validity through readability, understandability, interpretation, and cultural relevance. Participants (n = 288) were recruited from a convenience sample to assess: construct validity through exploratory factor analysis (EFA) using Promax rotation and maximum least squares extraction; and internal consistency using Cronbach’s α coefficient. Test-retest reliability was evaluated from the intraclass correlation coefficient (ICC2.1). Results: The forward-backward translation was achieved with eight items (1,3,4,5,9,11,12,22) modified and reformulated due to idiomatic issues. Internal consistency for the subscales ranged from α = 0.87–0.95, and the test-retest reliability was ICC(2,1)=0.92 (CI: 0.89–0.95). The EFA showed a four-factor solution, being identical to the original version, however items 20–22 loaded with items 23–26 in one factor, which was re-named “flexibility and social demand.” One item (#26) did not load above the required 0.30 threshold and was removed from the WRFQ-Pr. No floor or ceiling effects were found. Conclusions: The WRFQ translation and cross-cultural adaptation to Persian (WRFQ-Pr) was performed successfully. The determined properties of reliability and validity were comparable to those of the original English version.IMPLICATIONS FOR REHABILITATION The WRFW can simultaneously evaluate the health status of the worker, the existence of impairments, the involved factors in creating ability/disability at work, and the outcome of the interventions. There is no instrument available for the Persian-speaking population to evaluate related disability at work and the condition of return to work after a rehabilitation intervention. The WRFQ was translated and culturally adapted into Persian. The WRFW-Pr demonstrated excellent internal consistency, test-retest reliability and a four-factor structure.