Background Statins have been shown to possess anti-inflammatory and immunomodulatory effects. The objective of this study was to determine if preoperative statin therapy is associated with a reduced frequency of postoperative ARDS in surgical populations at increased risk of developing ARDS. Methods We performed a retrospective cohort evaluation of the association between preoperative statin therapy and early postoperative ARDS in patients undergoing elective high-risk thoracic and aortic vascular surgery. The association between preoperative statin therapy and postoperative ARDS was assessed using propensity-adjusted analyses to control for indication bias and confounding factors. Results Of 1845 patients, 722 were receiving preoperative statin therapy. 120 patients developed postoperative ARDS. Frequencies of ARDS among those receiving statin therapy versus those who were not was 7.2% and 6.1%, respectively (OR = 1.20, 95% CI = 0.83–1.75; p=0.330). Neither the stratified propensity score analysis (pooled OR 0.93; 95% CI = 0.60-1.43) nor matched analysis (OR = 0.78; 95% CI = 0.48-1.27) identified a statistically significant association between preoperative statin administration and postoperative ARDS. When compared to matched controls, patients who developed postoperative ARDS did not differ in mortality (7.7% versus 8.8%, p=0.51), hospital length of stay (21 days versus 15 days, p=0.21) or ventilator free days (24 days versus 25 days, p=0.62). Conclusions In patients undergoing high-risk surgery, preoperative statin therapy was not associated with a statistically significant reduction in postoperative ARDS. These results do not support the use of statins as prophylaxis against ARDS in patients undergoing high-risk surgery.