Objective To identify the incidence and risk factors of gastrointestinal bleeding in patients supported with mechanical ventilation over 48 hours. Method A total of 127 ICU patients supported with mechanical ventilation for over 48 hours were enrolled from January 1, 2007 to December 31, 2008 for the retrospective study. Exclusion criteria included the history of gastrointestinal bleeding and ulcer, recent gastrointestinal surgery, brain death and active bleeding from nose or throat. Demographics of patients including age, diagnosis at admission, duration of ICU stay, duration of mechanical ventilation, pattern and parameters of ventilation, ICU mortality, A-PACHE II score, multiple organ dysfunction score, and the results of biochemical assays including renal, hepatic and coagulation functions were recorded. Risk factors of gastrointestinal bleeding were analyzed by using univariate analysis And multiple logistic-regression analysis. Results Of the 127 patients, the incidence of gastrointestinal bleeding was 41.7% . and among them 3.9% patients suffered from clinically significant bleeding. However, the independent risk factors of gastrointestinal bleeding were the peak inspiratory pressure > 30 cmH20 (RR = 3.73, 95% CI = 1.59-9.46), renal failure (RR = 1.16,95% CI = 1.02 - 2.32), PLT count <50× 109 L-1(RR = 2.67, 95% CI = 1.32 - 15.78) and prolonged APTT (RR = 4.58, 95%CI = 2.32 - 12.96). The good entetal nutrition had a beneficial effect to the avoidance of gastrointestinal bleeding ( RR = 0.30, 95% CI = 0. 13 - 0.67). Conclusions The incidence of gastrointestinal bleeding is high in patients supported with mechanical ventilation, and the bleeding usually occurs within the first 48 hours. High pressure ventilator setting, renal failure, decreased PLT count and prolonged APTT are significant risk factors of gastrointestinal bleeding. However, the good enteral nutrition is the independent protective factors.