Myocardial bridge (MB) is a congenital abnormality where part of a coronary epicardial artery runs under the myocardium fibers and is compressed in systole; this becomes more pronounced when nitroglycerin (NTG) is administered. In this report, we describe the case of a 40-year-old African American man who presented with chest pain that did not respond to NTG or isosorbide mononitrate and was only partially relieved by narcotics. His past medical history was significant for coronary artery disease (CAD) with a stent into the left anterior descending artery (LAD) several months prior, hypertension, hyperlipidemia, paroxysmal atrial fibrillation, sick sinus syndrome, permanent pacemaker, pulmonary embolism, and cerebral vascular accident. No explanation for his angina was found either in the previous outpatient left heart catheterization (LHC) procedures demonstrating LAD stent patency or initial chest pain workup upon admission. Functional LHC procedure with adenosine infusion and acetylcholine provocation demonstrated endothelial dysfunction with notable epicardial spasm and MB of the LAD that worsened with NTG. Cardiology advised dual antiplatelet therapy and a statin as part of treatment for CAD and a calcium channel blocker with a bradycardic effect (e.g., diltiazem, verapamil) for the MB and coronary vasospasm, and avoidance of NTG and long-acting nitrates (e.g., isosorbide mononitrate), which can cause reflex tachycardia and worsen angina from MB. A selective serotonin reuptake inhibitor was added for increased cardiac nociception. The patient’s pain resolved, and he was discharged. MB is an important alternate etiology to consider when chest pain does not respond to NTG administration for adjustment of treatment modalities. The initial treatment for this patient’s pain with NTG likely exacerbated symptoms by reducing intrinsic coronary wall tension and subsequently increasing reflex sympathetic stimulation of contractility of the left ventricular myocardium, which can, in turn, increase anginal symptoms and ischemia.