Background The optimum timing to wean is crucial to avoid negative outcomes for mechanically ventilated patients. The rapid shallow breathing index (RSBI), a widely used weaning index, has limitations in predicting weaning outcomes. By replacing the tidal volume of the RSBI with diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) assessed by ultrasonography, we calculated two weaning indices, the diaphragmatic excursion rapid shallow breathing index (DE-RSBI, respiratory rate [RR]/DE) and the diaphragm thickening fraction rapid shallow breathing index (DTF-RSBI, RR/DTF). The aim of this study was to evaluate the predictive values of DTF-RSBI, DE-RSBI and traditional RSBI in weaning failure. Methods This prospective observational study included patients undergoing mechanical ventilation (MV) for > 48 h and who were readied for weaning. During a pressure support ventilation (PSV) spontaneous breathing trial (SBT), right hemidiaphragmatic excursion and DTF were measured by bedside ultrasonography as well as RSBI. Weaning failure was defined as: (1) failing the SBT and (2) SBT success but inability to maintain spontaneous breathing for more than 48 h without noninvasive or invasive ventilation. A receiver operator characteristic (ROC) curve was used for analyzing the diagnostic accuracy of RSBI, DE-RSBI, and DTF-RSBI. Results Of the 110 patients studied, 37 patients (33.6%) failed weaning. The area under the ROC (AUROC) curves for RSBI, DE-RSBI, and DTF-RSBI for predicting failed weaning were 0.639, 0.813, and 0.859, respectively. The AUROC curves for DE-RSBI and DTF-RSBI were significantly higher than for RSBI (P = 0.004 and P < 0.001, respectively). The best cut-off values for predicting failed weaning were RSBI > 51.2 breaths/min/L, DE-RSBI > 1.38 breaths/min/mm, and DTF-RSBI > 78.1 breaths/min/%. Conclusions In this study, two weaning indices determined by bedside ultrasonography, the DE-RSBI (RR/DE) and DTF-RSBI (RR/DTF), were shown to be more accurate than the traditional RSBI (RR/VT) in predicting weaning outcome during a PSV SBT.