BACKGROUND: Patients with heart failure experience severe and chronic physical and psychological manifestations while the disease progresses. Assessing the degree of distress caused by manifestations of the disease in patients is the first step in designing and evaluating intervention programs to improve patients’ symptoms. The aim of this study was to investigate the psychometric properties of the Persian version of the Symptom Distress Scale in HF patients. MATERIALS AND METHODS: This study was conducted via methodological research design from March to November 2019. The translation process and cross-cultural adaptation were performed using a process recommended by the World Health Organization. The face and content validity and internal consistency were used to evaluate the validity and reliability of the instrument. The scale was evaluated by exploratory and confirmatory factor analysis in 300 patients with heart failure, and the obtained data were analyzed using SPSS-22 and AMOS-22 software. RESULTS: The content validity of the scale was approved based on the results of the study. One-factor scale with 13 items was used in the confirmatory factor analysis, and the results showed that the instrument had high goodness-of-fit indices. Spearman correlation test for convergent validity showed a correlation between the score obtained by the Scale of Symptoms of Disease and the scores of The European Heart Failure Self-care Behavior scale (9 items) ( P < 0.0001). CONCLUSION: The Persian version of the Symptom Distress Scale can be used as a valid instrument for people with heart failure due to its desirable psychometric properties.