Introduction Care of the airway is an essential part of the management of patients receiving mechanical ventilation. If the airway is not properly managed, an endotracheal airway can result in retained secretions, airway obstructions, and infections. These complications may prolong mechanical ventilation durationand length of hospital stayand may increase the cost of affordability. Hypertonic saline nebulized suctioning is a technique used to lessen the duration of mechanical air flow and enhance airway clearance, which helps patients on mechanical ventilation breathe easier. Aim The objective of the study isto assess the effectiveness of nebulization with hypertonic saline on arterial blood gas parameters among mechanically ventilated patients. Methods The quasi-experimental design adopted with thirty-five mechanically ventilated samples was chosen using a non-probability purposive sample technique. Following the pre-test in the endotracheal tube, nebulization was given with 2 ml of hypertonic saline over 15-20 mins, two times each day, to the mechanically ventilated patients. Post-test was carried out about 15-20 minutes after the procedureusing arterial blood gas analysis results were obtained and interpreted. Results The study reveals that the p values corresponding to the arterial blood gas parameters PCo2, pO2, and HCo3 are less than 0.01 and are significant at a 1% level, and arterial blood gas(ABG) pHis less than 0.05 and is significant at a 5% level; hence there is a high significant difference between the pre-test and post-test mean scores of arterial blood gas parameters PCo2, pO2, HCo3, and ABG pH. Hence, the study concluded that nebulization with hypertonic saline for patients with mechanical ventilators is more effective in improving arterial blood gas parameters.