The hypothesis of this study states that in emergency department (ED) patients with non-traumatic symptomatic hypotension, the presence of hyperdynamic left ventricular function (LVF) is specific for sepsis as the etiology of shock. We performed a secondary analysis of patients with non-traumatic symptomatic hypotension enrolled in a randomized, clinical diagnostic trial. The study was done in an urban tertiary ED with a census over 100,000 visits per year. Inclusion criteria were non-trauma ED patients aged >17 years, initial vital signs consistent with shock (systolic blood pressure <100 mm Hg or shock index >1.0), and agreement of two independent observers for one sign and symptom of circulatory shock. All patients underwent focused ED echocardiography (echo) during initial resuscitation. Echos were reviewed post-hoc by a blinded physician and categorized by qualitative LVF as hyperdynamic (ejection fraction [EF] >55%), normal to moderate impairment (EF 30%-55%), and severe impairment (EF <30%). Main outcome was the criterion standard diagnosis of septic shock. Analyses include the diagnostic performance of LVF, Cohen's kappa for interobserver agreement of LVF, and logistic regression for independent predictors of sepsis. There were 103 echos that were adequate for analysis. The mean age was 57+/-16.7 years, 59% were male, and the mean initial systolic blood pressure was 83+/-11.3 mm Hg. A final diagnosis of septic shock was made in 38% (39/103) of patients. Seventeen of 103 (17%) patients had hyperdynamic LVF with an interobserver agreement of kappa=0.8. The sensitivity and specificity of hyperdynamic LVF for predicting sepsis were 33% (95% CI 19%-50%) and 94% (85%-98%), respectively. Hyperdynamic LVF had a positive likelihood ratio of 5.3 for the diagnosis of sepsis and was a strong independent predictor of sepsis as the final diagnosis with an odds ratio of 5.5 (95% CI 1.1-45). Among ED patients with non-traumatic undifferentiated symptomatic hypotension, the presence of hyperdynamic LVF on focused echo is highly specific for sepsis as the etiology of shock.