Sepsis remains a significant source of mortality among hospitalized patients. This study examines the usage of a vital sign-based screening protocol in identifying postoperative patients at risk for sepsis at an academic-affiliated medical center. We identified all general surgery inpatients undergoing abdominopelvic surgery from January to June 2014, and compared those with positive screening tests to a sample of screen-negative controls. Multivariate logistic regression was used to identify predictors of positive screening tests and progression to severe sepsis. In total, 478 patients underwent abdominopelvic operations, 59 had positive screening tests, 33 qualified for sepsis, and six progressed to severe sepsis. Predictors of a positive screening test were presence of cancer [odds ratio (OR) 30.7, 95% confidence interval (CI) 2.2-420], emergency operation (OR 6.5, 95% CI 1.7-24), longer operative time (OR 2.2/h, 95% CI 1.2-4.1), and presence of postoperative infection (OR 6.4, 95% CI 1.5-27). The screening protocol had sensitivity 100 per cent and specificity 88 per cent for severe sepsis. We identified no predictors of severe sepsis. In conclusion, vital sign-based screening provides value by drawing early attention to patients with potential to develop sepsis, but escalation of care for these patients should be based on clinical judgment.