Background/Objectives: Weaning failure remains a major challenge in patients requiring prolonged mechanical ventilation. This study aimed to describe outcomes in patients ventilated for >14 days and identify specific predictors of weaning success. Methods: A retrospective analysis of 88 patients from the Soroka University Medical Center database was conducted. Outcomes in the successful weaning (SW) group were compared to those in the failed weaning (FW) group. Predictors of weaning success were analyzed using multivariate logistic regression. Results: Forty patients (45%) were successfully weaned and discharged to rehabilitation or home. In-hospital mortality was 28%, with deaths occurring exclusively in the FW group (p < 0.001). One-month and one-year post-discharge all-cause mortality rates were 11% and 28%, respectively, with no group differences. Hypoalbuminemia and the Sequential Organ Failure Assessment (SOFA) score at admission significantly predicted weaning failure (odds ratio: 5.71 and 0.54, respectively). Demographics, comorbidities, ventilation indications, admission data, and diuretic use were not predictive. Conclusions: Hypoalbuminemia and the SOFA score at admission were key predictors of weaning success in patients ventilated for more than 2 weeks. Age and comorbidities were not significant. Prospective studies on albumin supplementation and high-protein diets are warranted to assess their impact on weaning outcomes.