The objective of the present study was to determine the reliability and validity of the Persian translation of the Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scales Young Adult Version in an Iranian sample of young adult patients with rheumatoid arthritis (RA). One hundred ninety-seven young adult patients with RA completed the 23-item PedsQL™ and the 36-item Short-Form Health Survey (SF-36). Disease activity based on Disease Activity Score 28 was also measured. Internal consistency and test-retest reliability, as well as construct, discriminant, and convergent validity, were tested. Confirmatory factor analysis (CFA) was used to verify the original factor structure of the PedsQL™. Also, responsiveness to change in PedsQL™ scores over time was assessed. Cronbach's alpha coefficients ranged from α = 0.82 to α = 0.91. Test-retest reproducibility was satisfactory for all scales and the total scale score. The PedsQL proved good convergent validity with the SF-36. The PedsQL distinguished well between young adult patients and healthy young adults and also RA groups with different comorbidities. The CFA did not confirm the original four-factor model, instead, analyses revealed a best-fitting five-factor model for the PedsQL™ Young Adult Version. Repeated measures analysis of variance indicated that the PedsQL scale scores for young adults increased significantly over time. The Persian translation of the PedsQL™ 4.0 Generic Core Scales Young Adult Version demonstrated good psychometric properties in young adult patients with RA and can be recommended for the use in RA research in Iran.