Coronary artery vasospasm (CVS), an uncommon cause of acute chest pain, can be provoked by vasoconstriction-induced medications. Misoprostol, a prostaglandin analog, is a safe medication to terminate a pregnancy. However, misoprostol can cause coronary artery vasospasm due to vasoconstrictor properties, leading to acute myocardial infarction with nonobstructive coronary arteries (MINOCA), especially in patients with a high risk for cardiovascular disease. We report a case of a 42-year-old female with a past medical history of hypertension who presented with ST-elevation myocardial infarction following the administration of a high-dose Misoprostol. The fact that coronary angiogram and intravascular ultrasound revealed normal coronary arteries suggested transient coronary vasospasm. CVS is a severe but rare cardiac adverse effect associated with high-dose misoprostol. This medication should be prescribed with caution and close monitoring, especially in those with pre-existing heart disease or cardiovascular risk factors. Our case raises awareness of severe cardiovascular complications that can be related to using misoprostol in high-risk patients.