Background: Ineffective parental antibiotic use in management of Ventilator associated pneumonia (VAP) open the window for using inhaled antibiotic formula to achieve higher local concentration of antibiotics and subsequently good recovery response. Objectives: This work was aimed to evaluate the aerosolized antibiotics (Colistin and Gentamicin) efficacy in improving the mechanically ventilated patient as adjunctive to intravenous systemic antibiotics.    Patients and Methods: This randomized control (RCT) trial study included a total of thirty mechanically ventilated patients, attending at Respiratory Intensive Care Unit (RICU), Chest Diseases Department, Faculty of Medicine, Ain Shams University Hospitals. They were classified equally into three groups; Group I: involved 10 patients who received aerosolized Colistin along with systematic antibiotics (SA), group II: involved 10 patients who received aerosolized Gentamicin along with SA and group III (Control): involved 10 patients who received only SA. Results: The incidence of VAP was 10%; in group I no cases had VAP, while in group II and controls, just (20 %) and (10 %) of cases had VAP respectively, with insignificant association of VAP with particular group, (P= 0.3). Clinically; only group I showed significant lower degree of temperature in comparison with controls, (P= 0.01). The mean days of MV and ICU in each group were (6.8±2.15; 8.9±3.11, 5.9±2.23; 7.2±2.7, 5.1±1.1; 6.1±1.85) respectively, with insignificant difference between the treatment groups. Finally, the survival rate in group I was 90 %, and was slightly lower in group II and control group; 60 % and 50 % respectively, with insignificant association of survival status in particular group. Conclusion: It could be concluded that the empirical treatment by aerosolized Colistin was more effective as an adjunctive therapy to SA for VAP protection than aerosolized Gentamicin, it had rapid resolution of respiratory infection signs, and subsequently the MV days, ICU stays and cost but had no effect on mortality.