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Coronary artery spasm (CAS) is a dangerous complication during cardiac surgery, causing arduous weaning of extracorporeal circulation (ECC) and myocardial tissue loss with consequent left and right ventricular dysfunctions. We describe the case of a 67-year-old man with hypertension and smoking habit, with ECG evidence of lateral myocardial ischemia without symptoms. On this basis, he was investigated with scintigraphy, which confirmed an anterior-lateral area of reversible ischemia and, subsequently, with angiography, which revealed just mild lesion (50%) of diagonal ramus associated with ascending aorta aneurysm: no sign of CAS was detected. Left ventricular function was normal, with mild hypokinesia of the apical segments and trivial aortic regurgitation. The patient underwent ascending aorta replacement with arduous ECC weaning due to CAS: exclusively, the use of intravenous administration of diltiazem led to the solution of this complication. Even if medical therapy is generally efficacious for this complication, the diagnosis is very complicated when it appears in the operating room immediately after cardiac surgery because of the lack of any useful device. The difficulty of diagnosis in the operating room might compromise patient outcome. In our opinion, when ECC weaning is complicated by several episodes of malignant tachyarrhythmia and there is the suspicion of underlying ischemic cause without other obvious causes, CAS must be considered and empirical therapy with calcium channel blockers should be used.