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Background: The CHA₂DS₂-VAS_C score is used to predict the risk of thromboembolic complications in patients with atrial fibrillation (AF). We hypothesized that the CHA₂DS₂-VAS_C score can be used to predict mortality in patients undergoing coronary angiography. Methods and Results: This was a prospective study of 990 patients undergoing coronary angiography. The median follow-up was 2294 days. The patients were categorized into two groups according to their CHA₂DS₂-VAS_C score: group I had scores <4 and group II had scores ≥4 (527 (53.2%) and 463 (46.8%), respectively). A Kaplan–Meier analysis demonstrated a significant association between the CHA₂DS₂-VAS_C score and mortality (69/527 (13.1%) vs. 179/463 (38.7%) for group I vs. group II, respectively, <i>p</i> < 0.0001). The association remained significant in patients with and without AF, reduced and preserved LVEF, normal and reduced kidney function, and with and without ACS (<i>p</i> < 0.009 to <i>p</i> < 0.0001 for all). In the Cox regression model, which combined the CHA₂DS₂-VAS_C score, the presence of AF, LVEF, anemia, and renal insufficiency, an elevated CHA₂DS₂-VAS_C score of ≥4 was independently associated with higher mortality (HR 2.12, CI 1.29–3.25, <i>p</i> = 0.001). Conclusions: The CHA₂DS₂VAS_C score is a simple and reliable mortality predictor in patients undergoing coronary angiography and should be used for the initial screening for such patients.