Objectives To determine if hemodynamic changes secondary to propofol administration are a result of direct myocardial depression as measured by global longitudinal strain (GLS). The authors hypothesized that propofol would cause a significant worsening in GLS, indicating direct myocardial depression. Design Prospective, observational. Setting Endoscopy suite at a single academic medical center. Participants Patients undergoing outpatient, elective endoscopic procedures at an outpatient clinic of a single tertiary care academic medical center. Interventions None. Measurements and Main Results Limited transthoracic echocardiograms were performed before and after patients received propofol for endoscopic procedures. Post-processing measurements included GLS, 2D (dimensional) ejection fraction (2D EF), and 3D EF. Using paired sample Student’s t test, no statistically significant change in GLS, 2D EF, or 3D EF was found despite statistically significant hypotension. In fact, there was a trend toward more negative GLS (improved myocardial function) in patients after receiving propofol. Conclusion We found propofol did not cause a reduction in systolic function as measured by GLS, a sensitive measure of myocardial contractility. Therefore, decreases in blood pressure after a propofol bolus in spontaneously breathing patients are likely due to decreased vascular tone and not impaired left ventricular systolic function. These results should be considered in the management of propofol-induced hypotension for spontaneously breathing patients.