Impaired glucose metabolism is an established risk factor for coronary artery disease. Previous studies revealed that glycemic variability (GV) is also important for glucose metabolism in patients with acute coronary syndrome (ACS). We explored the association between GV and prognosis in patients with ACS. A total of 417 patients with ACS who received reperfusion wore a continuous glucose monitoring system (CGMS) in a stable phase after admission and were monitored for at least 24 consecutive h. The mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. We divided into two groups based on the highest tertile levels of MAGE (MAGE = 52 mg/dl). The groups were followed up for a median of 39 months [IQR 24–50 months]. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE). During follow-up, 66 patients experienced MACCE (5 patients had cardiovascular death, 14 had recurrence of ACS, 27 had angina requiring revascularization, 8 had acute decompensated heart failure, and 16 had a stroke). MACCE was more frequently observed in the high MAGE group (23.5% vs. 11.6%, p = 0.002). In multivariate analysis, high MAGE was an independent predictive factor of poor prognosis for MACCE (odds ratio, 1.84; 95% confidence interval, 1.01–3.36; p = 0.045). Glycemic variability determined with a CGMS is a predictor of prognosis in patients with ACS without severe DM. Trial registration UMIN 000010620. Registered April 1st 2012