Background: Stress ulcers are common in mechanically ventilated patients. They are the most common cause of gastrointestinal bleeding and are primarily associated with increased the consumption of non-steroidal anti-inflammatory drugs. Despite advanced treatment, it has a high in-hospital mortality rate. This study assessed the effect of fenugreek (Trigonella foenum-graceum L.) seeds on gastrointestinal bleeding in mechanically ventilated patients.Methods: In this double-blind, randomized controlled clinical trial, 60 mechanically ventilated patients hospitalized in intensive care units were equally distributed into intervention and control groups. The intervention group received 3 mg fenugreek seeds powder twice daily with a gavage solution for five days, in addition to routine treatment. The control group received only the gavage solution and routine treatment. The gastrointestinal bleeding and abdominal pain at admission and during the five days were assessed. Data were analyzed using SPSS software V. 16, and the significance level was set at 0.05. Results: Gastrointestinal bleeding at admission was similar in both groups. The number of mechanically ventilated patients with gastrointestinal bleeding decreased on the third, fourth, and fifth days, but the difference was insignificant. The Cochran test results showed that the rate of stress-induced gastroin-testinal bleeding in the control group increased significantly (P =.04). The decrease in gastrointestinal bleeding in the intervention group was not statistically significant (P=.08). Conclusion: The use of this drug reduces the gastrointestinal side effects of ventilated patient. Despite this, reducing gastrointestinal bleeding and similar mechanical ventilation complications in patients entirely dependent on the treating team is an important achievement.