The parasternal intercostal muscle activity, a marker of accessory muscle usage, is found to correlate inversely with the pressure-generating capacity of the diaphragm and level of support of mechanical ventilation. The primary objective of our study was to determine whether the parasternal intercostal muscle thickening fraction (PMTF) measured by ultrasonography can predict weaning. We also evaluated whether addition of lung ultrasound score and echocardiographic assessment can add on to predicting weaning failure. This prospective observational study conducted in a mixed medical-surgical intensive care unit, included 60 adult patients who were eligible for a spontaneous breathing trial (SBT) after being invasively mechanically ventilated for more than 48 hours. Ultrasound of respiratory muscles, lung parenchyma, and echocardiographic assessment were performed before and after 120 minutes of SBT. Parasternal intercostal muscles were imaged with a high frequency linear probe on the right second intercostal space 5 cm lateral to the sternal margin. PMTF was calculated as (maximum-minimum thickness)/minimum thickness. Among 60 patients, SBT failure was seen in 11 patients and extubation failed in 8 patients. PMTF (%) was significantly higher in the weaning failure group (13.33 [8.33-19.05]) as compared to patients with successful weaning (6.67 [6.06-11.54]). Diaphragmatic thickening fraction (DTF) correlated inversely to PMTF in patients with weaning failure. A pre-SBT PMTF cut-off of ≥7.7% and post-SBT cut-off of ≥15.38% were good predictors of weaning failure and extubation failure, respectively. PMTF has good discriminatory power to predict weaning outcomes (area under the receiver operating characteristic curve: 0.74 [0.59-0.88]). Pre-SBT PMTF had similar power as DTF to predict weaning failure.