Multivessel or multisegment spasm in patients with known widespread coronary atherosclerotic disease is an infrequent occurrence. We describe a prolonged spasm of both the left main and the left anterior descending artery in a patient with chronic effort angina and multivessel coronary artery disease, who previously underwent percutaneous coronary intervention and drug eluting stents implantation. The patient complained of episodes of angina and palpitations, mainly at rest. Exercise stress test resulted positive in therapeutic wash-out. Coronary angiography was performed which showed: 80% stenosis in the proximal segment of the Left Main (LM) and the mid Left Anterior Descending artery (LAD), 90% stenosis of the Posterior Descending Artery (PDA); there was no angiographic evidence of instent restenosis in the previously stented segments. Coronary Artery By-pass Graft (CABG) was proposed, but the patient refused surgery. Reperfusion strategy included coronary angioplasty of the LM and the LAD. Before the procedure, in the presence of ischemic EKG changes, nitrates were infused in the left coronary artery with resolution of both the LM and LAD stenoses. However, intracoronary nitrates in the right coronary artery did not resolve the PDA stenosis. The patient underwent angioplasty and stenting of the PDA alone. Selective spasm involving two anatomically different segments is rare. The left main location is critical since it can lead to unnecessary coronary artery by-pass. Intracoronary nitrates should be administered before invasive strategies are advised.