Background: The Post-Liver Transplant Quality of Life (PLTQ) instrument is a specific, disease-based questionnaire to evaluate health-related quality of life (HRQOL) of liver transplantation (LTx) recipients. The aim of this study is translation, cross-cultural adaptation, and evaluation of the psychometric properties of the Persian version of PLTQ (PV-PLTQ) questionnaire.Methods: All of the stages of translation and cross-cultural adaptation of the original PLTQ instrument was carried out according to the published guideline. A total of 175 LTx recipients completed the PLTQ and short form-36 (SF-36) questionnaires. Sixty-eight randomly selected patients were asked to complete the PLTQ, 2 to 3 months later. Face validity, content validity, acceptability internal consistency, test-retest reliability, sensitivity to change, and convergent validity were evaluated.Results: The results of face validity, content validity, and missing data proportion indicate that PV-PLTQ questionnaire is acceptable and easy to understand. Cronbach’s alpha coefficient for the PV-PLTQ questionnaire was 0.97 (0.82 to 0.95) for domains. The results of test-retest reliability show moderate to good intraclass correlation coefficient from 0.6 to 0.86 (P< 0.05). Also, the results of the Kruskal-Wallis test shows that this questionnaire is sensitive to HRQOL changes. The correlations between PV-PLTQ domains and physical and mental components of SF-36 present a good convergent validity (P< 0.05).Conclusio: In general, The PV-PLTQ questionnaire is a valid, reliable and sensitive to change instrument to evaluate HRQOL in LTx recipients and can be applied in further researches and clinical settings in the Persian speaking population.