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Deep venous thrombosis (DVT) is common in intensive care unit (ICU) patients. It is often silent and may be complicated by pulmonary embolism and death. Thromboprophylaxis with heparin does not always prevent venous thromboembolism (VTE). Aspirin (ASA) reduces the risk of VTE in surgical and high-risk medical patients but it is unknown if ASA may prevent DVT in mechanically ventilated ICU patients. We performed a retrospective chart review of critically ill patients who received mechanical ventilation for >72 h and underwent venous ultrasonography for suspected DVT between Jan 2012 and Dec 2013. We excluded patients who were on therapeutic doses of anticoagulation or had coagulopathy. We used multivariable logistic regression to evaluate association between aspirin use and DVT during hospitalization. There were 193 patients. The mean ± SD age was 58 ± 15.7 years. Half were male. DVT was found in 49 (25.4%). DVT was found in the first 15 days of hospitalization in 67.3% of the patients. The majority (82.8%) received thromboprophylaxis with unfractionated or low molecular weight heparin. Fifty-six (29%) were on ASA. On multivariable regression analysis, ASA use was associated with a significant reduction in the odds of finding DVT (OR 0.39, 95% CI 0.16-0.94; p = 0.036). DVT is common in mechanically ventilated ICU patients despite the use of thromboprophylaxis. Aspirin may prevent DVT in such patients.