Bitter orange (Citrus aurantium) extract and its primary protoalkaloidp-synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance.p-Synephrine is also present in juices and foods derived from a variety ofCitrusspecies. Questions exist regarding the safety ofp-synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49-mgp-synephrine) given to 18 healthy subjects (nine men and nine women) in a double-blinded, placebo-controlled cross-over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4, 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, andp-synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control orp-synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in thep-synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants.p-Synephrine does not act as a stimulant at the dose used. Copyright © 2016 John Wiley & Sons, Ltd.