Background and Objectives: In patients with acute coronary syndrome, electrocardiographic parameters, including ST elevation in lead aVR (aVR-STE), ST depression (aVR-STD), and QTc prolongation, are crucial. This study aims to show the predictive value of a longer QTc in emergency department patients with acute coronary syndrome and ≥1 mm ST elevation or depression in the aVR lead in electrocardiography. Materials and Methods: A retrospective analysis was conducted on 1273 patients admitted to the emergency department with a preliminary diagnosis of acute coronary syndrome between 2020 and 2023. ST depression, ST elevation, and QTc were documented in the electrocardiography of the patients. Furthermore, acute coronary syndrome subtypes were identified. Basic demographic characteristics, complications, concomitant diseases, and 30-day and 180-day mortality data were collected. Results: The mean age of 1273 patients included in the study was 63.23 (10.06) years and 548 (43%) were female (p = 0.030). In the aVR-STE group, the QTc was 483.31 (33.96) ms in STEMI, 474.98 (26.21) ms in NSTEMI, and 505.60 (9.76) ms in those with mortality (p < 0.001). In the aVR-STD group, the QTc was 465.10 (42.63) ms in STEMI, 457.52 (39.52) ms in NSTEMI, and 508.73 (4.71) ms in those with mortality (p < 0.001). The total 30-day mortality was 129 (10.1%) and 180-day mortality was 181 (14.2%) (p < 0.001). In the uni-multivariable regression analysis performed for both change in aVR derivation and mortality, it was determined that prolonging QTc could be a predictive value for acute coronary syndrome (p < 0.001). We found sensitivity at 99.7% and specificity at 99.2% in predicting mortality in patients with prolonged QTc (AUC: 0.983, 95% CI: 0.974–0.993, p < 0.001). Conclusions: In patients with acute coronary syndrome, a prolonged QTc is an independent predictor of short- and long-term mortality in alterations in aVR derivation.