Ventilator-associated pneumonia (VAP) is accompanied with serious complications. The current study assessed the impact of adjuvant nebulized colistin on the outcomes of VAP patients. The study was a prospectively randomized clinical controlled trial done at the international medical center, Cairo, Egypt on VAP. Patients presenting with infection ≥ 48 hours of mechanical-ventilation (MV) with age ≥ 18 years were included. Patients were excluded when presenting with documented bronchiectasis, cystic fibrosis, known allergy to polymyxin or with creatinine clearance less than 30ml/min. Eligible patients were randomly assigned to: Control group (20); received empiric IV antibiotic therapy or Test group (20); received an empiric IV antibiotic therapy with adjunctive nebulized colistin three times daily for 7 days. At baseline, both groups were subjected to full data collection, laboratory investigations (CBC, ABG, renal and liver function tests) severity scores (APACHE, SOFA) and chest X-rays. Vital signs, ventilatory status, PaO2/FiO2 (P/F ratio), 30- day mortality, weaning off MV and occurrence of complications were all assessed through the study. Groups were comparable at baseline. APACHE and SOFA scores, WBC count, P/F ratio, mode of MV, fraction of inspired O2 (FiO2) all significantly improved (p < 0.005) in the test versus control groups. Test group improved in weaning off MV, percentage of negative culture and number of deaths (p < 0.05) versus control. Adjunctive nebulized colistin improved the severity scores, APACHE and SOFA, ventilatory parameters and oxygenation with better weaning off MV. It resulted in improved bacteria eradication, chest X-ray finding and ICU death when compared with conventional therapy.