This study aimed to assess the ability of lung ultrasound (LUS) to predict mechanical ventilation (MV) weaning outcomes in critically ill adults. Methods: A prospective observational study that analyzed data collected from 50 adult patients, mechanically ventilated for more than 48 hours and eligible for their first spontaneous breathing trial. A LUS was performed prior to and at the end of a 1-hour SBT. To quantify lung aeration, a LUS score was calculated. Patients were divided into two groups according to their response to weaning trials with group A showing successful weaning while group B showing failed weaning. All included patients were followed up to Intensive Care Unit discharge. Results: Weaning failure was observed in 36% of patients. LUS score showed a significant difference between both groups (P < 0.001). Pre- and post-SBT LUS scores were significantly higher in the failed weaning group (14.44 ±2.52 and 18.83 ±3.18 respectively) than in the successful weaning group (11.25 ±3.05 and 12.53 ±3.41 respectively). A ROC analysis for the ability of post-SBT LUS score to predict weaning outcomes revealed a significant AUC of 0.911 with a 95% confidence interval ranging from 0.830-0.992 (P < 0.0001). The best cut-off was 14.5, at which sensitivity and specificity were 88.8% and 68.7%, respectively. Conclusions: Our data suggest that LUS can be used as a predictor of MV weaning outcomes in critically ill adults. A post-SBT LUS score cut-off value of 14.5 has a sensitivity and a specificity of 88.8% and 68.7%, respectively.