OBJECTIVE To report a case of acute myocardial infarction (MI) associated with the use of oral sildenafil in a nitrate-free patient. CASE SUMMARY A 45-year-old man was admitted to the hospital with acute left-sided chest pain, nausea, and vomiting that started approximately 30 minutes after taking sildenafil 100 mg before a sexual contact. The patient was diagnosed with an acute anterior MI, and therapy with aspirin, metoprolol, and unfractionated heparin was initiated. Early coronary reperfusion treatment with primary percutaneous transluminal coronary angioplasty was performed after initial evaluation. Balloon angioplasty followed by coronary stenting was performed successfully in the 80%-occluded left anterior descending artery. The patient was discharged one week after the coronary intervention without complication. DISCUSSION Sildenafil-associated MI is rarely seen in patients without documented coronary artery disease. By inhibiting phosphodiesterase type 5, sildenafil can cause an increase in cyclic guanosine monophosphate levels, which mediates the relaxation of vascular smooth muscle in the corpus cavernosum. Although sildenafil can cause a major decline in systemic arterial pressure in the existence of organic nitrates, physicians should be aware of its adverse cardiovascular effects even in nitrate-free patients. The Naranjo probability scale indicates that sildenafil was the possible cause of the MI. CONCLUSIONS Sildenafil may rarely be associated with MI in patients with no known cardiac history. Physicians should be aware of this rare and serious adverse reaction to sildenafil and counsel patients not to take sildenafil before undergoing a complete physical evaluation and further testing if warranted.