Study objectives: To define a set of orthostatic vital signs that minimize the frequency of false-positives among healthy individuals while maximizing sensitivity in detecting acute moderate blood loss and to determine the sensitivity and specificity of this optimized tilt test in detecting acute moderate blood loss. Design and intervention: Postural vital signs were recorded in a standardized manner before and after 450-mL phlebotomy. Paired comparisons were done for a variety of criteria for a positive tilt test using receiver-operating characteristic curves. Setting and type of participants: Three hundred forty-five healthy euvolemic adult volunteer blood donors were tested at three community blood donation centers over a one-year period. Subjects were prospectively divided into group 1 (less than age 65; 301) and group 2 (age 65 or older; 44). Measurements and main results: For each combination of pulse and blood pressure in group 1, a change in pulse alone had the same or higher sensitivity with at least the same specificity. Pulse alone was similarly superior in group 2 compared with previously published combinations of pulse and blood pressure. Even the optimized tilt test had limited sensitivity in detecting acute moderate blood loss with high specificity. Conclusion: In applying the tilt test to young adults without cardiovascular disease, pulse measurement usually is all that is necessary. [Witting MD, Wears RL, Li S: Defining the positive tilt test: A study of healthy adults with moderate acute blood loss. Ann Emerg Med June 1994;23:1320-1323.].