BACKGROUND There is a scarcity of externally valid data that investigate the utility of operative time, a common clinical parameter, as a predictor of free flap failures. Our aim was to assess whether prolonged operative time correlates with early flap failure following free tissue transfer in the acute care setting using the American College of Surgeons National Surgical Quality Improvement Program database. METHODS The 2005-2011 American College of Surgeons National Surgical Quality Improvement Program databases were reviewed for encounters that entailed a free tissue transfer via a CPT algorithm. Patients identified as having a flap loss were compared with people who did not with regards to operative time and patient comorbidities. Patients were subdivided into the following cohort groups with regards to operative time: <6 hours, 6-12 hours, and >12 hours. Secondary outcome was association between increasing operative time and postoperative complications. RESULTS Of the 2,008 patients identified, 62 (3.1%) had early flap failure. After multivariable analysis, it was found that progressive operative time was associated with an increased risk of flap failure; 6-12 hours odds ratio was 4.64 and >12 hours odds ratio was 5.65 (P = 0.0140). Higher American Society of Anesthesiologists class (P = 0.0042) was also shown to be significantly associated with flap failure. On secondary analysis, increasing operative time was correlated with the following complications: pneumonia, blood transfusions, prolonged ventilation, wound dehiscence, and wound complications. CONCLUSIONS Our results, one of the largest series in the literature, revealed that prolonged operative time was associated with a stepwise increase in the likelihood of early flap failure as well certain postoperative complications. © 2014 Wiley Periodicals, Inc. Microsurgery 37:12-20, 2017.