Background <p>With the increasing prevalence of psychiatric illnesses, the need for family members to assume caregiving roles at home has grown significantly in recent years. One of the most significant and multidimensional negative outcomes for these caregivers is the caregiving burden. This study aimed to evaluate the psychometric properties of the Persian version of the 12-item Zarit Burden Interview (ZBI-12) among family caregivers of patients with chronic psychiatric conditions.</p> Methods <p>This methodological study was conducted in 2024 on 400 family caregivers of patients with chronic psychiatric disorders in Mashhad, Iran, using convenience sampling. Following translation and approval for use, face and content validity of the ZBI-12 were assessed through both qualitative and quantitative methods, including impact scores, content validity index and ratio, and modified kappa statistics. Construct validity was examined using exploratory factor analysis (EFA; <i>n</i> = 200) and confirmatory factor analysis (CFA; <i>n</i> = 200), followed by assessment of convergent and discriminant validity using the Fornell and Larcker approach. Internal consistency was evaluated using Cronbach’s alpha, construct reliability (CR) and McDonald’s omega, while stability was assessed via the intraclass correlation coefficient (ICC).</p> Results <p>No items were removed during the validity assessment process. EFA revealed two underlying factors (Burnout and Responsibility) accounting for 63.94% of the total variance in caregiving burden. CFA confirmed a good model fit. Both factors demonstrated acceptable convergent and discriminant validity. Reliability analyses showed that Cronbach’s alpha, CR, McDonald’s omega, and ICC values indicated strong internal consistency and stability.</p> Conclusion <p>The findings suggest that the Persian version of the ZBI-12 is a valid and reliable instrument for assessing caregiving burden among family caregivers of individuals with psychiatric disorders in Iran.</p>