BACKGROUND: "Persian Weaning Tool" (PWT) is the only specific, national protocol designed to assess patients' readiness for weaning from mechanical ventilation in Iran. This study was developed to determine the validity and reliability of this protocol. MATERIALS AND METHODS: This is a psychometric study conducted on 31 patients connected to mechanical ventilation were ready from weaning according to anesthesiologist's diagnosis and was selected through convenient sampling. The patients selected from Intensive Care Units (ICUs) of Al-Zahra Hospital in Isfahan. The sheet data collection includes demographic data, PWT; Burn's Wean Assessment Program (BWAP), and Morganroth's scale. To determine the inter-rater reliability between researcher and his partner, Pearson correlation and paired t-test were used. To assess the criterion validity of the PWT in relation to Burn's and Morganroth's weaning scales (as criteria), Pearson correlation and McNemar tests were used. To specify a minimum acceptable score of the PWT for weaning from mechanical ventilation, receiver operating characteristic curve was used. RESULTS: The results showed that there was statistically significant correlation between score of PWT and BWAP (r = 0.370 with P < 0.05) and there were no statistically significant differences between these tools in terms of identification of patients' readiness for weaning (P = 0.453). There was statistically significant correlation between PWT score obtained by researcher and his colleague (r = 0.928), and the reliability of this tool was approved. The PWTs cut of point was calculated as 57 (sensitivity = 0.679, specificity = 1). CONCLUSIONS: The reliability and validity of the PWT were confirmed for this study's sample size. Consequently, the findings of this study can be used to measure the PWTs effectiveness and applicability in ICUs.