Background and Objective: Hypoxia is a major problem in patients undergoing ventilation due to the high bronchioles secretion. This study aimed to determine the effect of expiratory rib-cage compression prior to endotracheal suctioning on arterial blood oxygenation (SpO2) in patients undergoing mechanical ventilation. Materials and Methods: This clinical trial with a crossover design included 50 mechanically ventilated patients hospitalized in the intensive care units of two educational hospitals (Vali-e-Asr and Ayatollah Mousavi) of Zanjan using the convenience sampling method. The participants were randomly divided into two groups. During the first phase of the study, the rib-cage compression was performed once for five minutes prior to suctioning in group one. The other group received suctioning without any rib-cage compression. The procedures were performed in a reverse fashion in the two groups after three hours. SpO2 was measured three times: five minutes prior to the endotracheal suctioning, and 15 and 25 minutes following the procedure. Data were analyzed using independent and paired t-tests. Results: There were statistically significant differences in the SpO2 mean values between five minutes before and 15 minutes after the endotracheal suctioning in patients who received endotracheal suctioning with the rib-cage compression (P< 0.05). Moreover, there was a statistically significant difference between the mean SpO2 values in the same intervals between the two groups (P< 0.0001). Conclusion: The results show that expiratory rib-cage compression prior to endotracheal suctioning improves arterial blood oxygenation in patients undergoing mechanical ventilation. Therefore, we recommend performing the procedure.