Appropriate diagnosis of patients with chest pain and no significant angiographic coronary artery disease remains challenging. We present the case of a 65-year-old woman with recurrent chest pain that was triggered by exertion as well as emotional stress. She underwent coronary angiography and intravascular ultrasound which demonstrated no atherosclerosis. Coronary flow reserve assessment was also normal suggesting no significant microvascular disease. Intracoronary infusion of acetylcholine, however, resulted in an increase in blood velocity and epicardial vasoconstriction, confirmed by chest pain, electrocardiogram changes and complete closure of a coronary artery by angiography, suggesting the diagnosis of coronary vasospasm or variant angina. This report highlights the importance of considering vasoconstriction when markedly increased blood velocity is observed in response to acetylcholine.