Patients with artificial airways are considered at high risk for aspiration. An endotracheal tube [ETT] is the most commonly used artificial airway. Despite its benefit for providing airway management for critically ill patients, it may be associated with problems and complications that may be life threatening. Objective: This study was conducted to determine the effect of utilization of nursing practice guidelines on occurrence of aspiration for critically ill intubated patients. Design: A quasi-experimental design. Sample: Forty critically ill intubated adult patients. Method: An assessment of the nurses' knowledge and skills to prevent occurrence of aspiration was initially performed. Observation was done first for nurses involved in providing direct patient care for the control group after 24 hours of intubation. Then implementation of the developed guidelines on the study group after instruction of these guidelines in the second day of intubation and followed up for seven consequent days. Assessment of the occurrence of aspiration among the control and study groups was done. Patients were followed up from the second day of intubation up to seven consequent days to detect aspiration's manifestations and chest X-ray changes. Comparison between the control and study groups was done to determine the effect of the use of the nursing practice guidelines on occurrence of aspiration. Results: Marked improvement in the nursing practices was found after instructions for the nursing guidelines. The results of the study revealed decrease in the percent of aspiration manifestations. Moreover, it was observed that there were some possible contributing factors for pulmonary aspiration such as age, Glasco coma scale, and the mode of ventilator. Conclusion: The results of present study highlighted the importance of the nursing role in prevention of aspiration. The intubated patient requires meticulous care to ensure airways maintenance and prevent complications until he can maintain independent ventilation.