Background The ability of focused assessment with sonography for trauma (FAST) to detect clinically significant hemorrhage in hypotensive injured patients remains unclear. We sought to describe the sensitivity and specificity of FAST using findings at laparotomy as the confirmatory test. Methods Patients from the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study that had a systolic blood pressure < 90mm Hg and underwent FAST were analysed. Results were compared with findings at laparotomy. A therapeutic laparotomy (T-LAP) was defined as an abdominal operation within 6 hours in which a definitive procedure was performed. The sensitivity and specificity of FAST were calculated. Results The cohort included 317 patients that underwent FAST (108 positive, 209 negative). T-LAP was performed in 69% (n=75) of FAST(+) patients and 22% (n=48) of FAST(-) patients. FAST had a sensitivity of 62% and specificity of 83%. Conclusions In our multicenter cohort, 22% of FAST(-) patients underwent T-LAP within 6 hours of admission. In hypotensive patients with a negative FAST, clinicians should still maintain a high index of suspicion for significant abdominal hemorrhage. Level of evidence Level IV.