Introduction: Non-ST-elevation (NSTE) acute coronary syndrome (ACS) is a common and polymorphic condition. Predicting significant coronary artery disease (CAD) is sometimes difficult. The objective of this study was to identify predictors of CAD severity in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Patients and Methods: We prospectively evaluated 296 patients with NSTE-ACS who underwent a coronary angiography. Significant CAD was defined as ≥70% stenosis in at least one major coronary artery. Clinical characteristics in the hospital for 30 days and one-year outcomes were prospectively noted and a multivariate analysis was performed. Results: The study included 296 NSTE-ACS patients. The mean age of the patients was 62.1 ± 12.6 years old while 58.1% of the patients were males. A multivariable analysis for the significant CAD predictors is shown (Figure 1), representing current smoking (ORa = 4.4; 95% confidence interval [CI] = 1.5–13.0, p = 0.007), a diabetic under insulin (Ora = 6.4; 95% [CI] = 2.4–17.4, p < 10-3), typical angina (ORa = 5.4; 95% [CI] = 1.7–16.8, p = 0.003), persistent angina (ORa = 5.3; 95% [CI] = 1.3–21.8, p = 0.019), recurrence of angina (ORa = 8.9; 95% [CI] = 1.5–51.4; p = 0.015), down sloping ST depression (ORa = 6.1; 95% [CI] = 2.4–15.3, p < 10-3), positive troponin (ORa = 4.2; 95% [CI] = 1.9–9.2, p < 10-3), kinetic disorder > 2 segments (ORa = 2.5; 95% [CI] = 1.1–6.0, p = 0.049), intima-media thickness (IMT) > 0.8 mm (ORa = 5.2; 95% [CI] = 2.3–12.1, p < 10-3). Conclusion: In this study, the severity of CAD was predicted by parameters such as typical or recurrent angina pectoris, current smoking, diabetic on insulin, down sloping ST depression, elevation of troponin, kinetic anomaly in more than two segments and the IMT greater than 0.8 mm.