Background: Rapid shallow breathing index (RSBI) is a well-known weaning index. However; its diagnostic performance is less than satisfactory. Recently, diaphragmatic rapid shallow breathing index (DRSBI) is proposed as a promising tool in weaning outcome prediction. The aim of this study was to evaluate if DRSBI is more accurate than RSBI for weaning outcome prediction. Patients and methods: This prospective, randomized clinical trial was carried out on 106 mechanically ventilated patients for more than 48 h and ready to wean at their first spontaneous breathing trial (SBT). After one minute of SBT, RSBI and DRSBI were calculated. According to the decision to continue SBT patients were divided into: Group I (53 patients) the decision depends on the RSBI. Group II (53 patients) the decision based on DRSBI. 30 min later, patients were reevaluated for tolerance of SBT then RSBI and DRSBI were calculated. Outcome of the weaning attempt was recorded and ROC analysis was done to evaluate the diagnostic accuracy. Results: 106 patients were enrolled. Trauma was the commonest diagnosis on ICU admission and traumatic brain injury was the main indication for initiation of mechanical ventilation in the two groups. 33 patients (31.1%) failed to wean (19 patients in group I and 14 patients in group II). RSBI at 1 min and 30 min as well as DRSBI at 1 min and 30 min were highly statistical significant higher in weaning failure patients. RSBI and DRSBI at 30 min were highly statistical significant increased compared to at 1 min. DRSBI at 30 min was the parameter with the best diagnostic accuracy for predicting weaning success with a cutoff value <1.6 breaths/ min/mm. Conclusion: DRSBI has a better diagnostic accuracy than the traditional RSBI in predicting weaning outcome specially when monitored at 30 min from the start of SBT. Trial registration: this clinical trial was registered with ClinicalTrials.gov (NCT03561792)