Background Several risk scores were developed for acute coronary syndrome (ACS) patients, but their use is limited by their complexity. Purpose The purpose of this study was to identify predictors at admission for in-hospital mortality in ACS patients in western Romania, using a simple risk-assessment tool – the new Canada acute coronary syndrome (C-ACS) risk score. Patients and methods The baseline risk of patients admitted with ACS was retrospectively assessed using the C-ACS risk score. The score ranged from 0 to 4; 1 point was assigned for the presence of each of the following parameters: age ≥75 years, Killip class >1, systolic blood pressure <100 mmHg, and heart rate >100 bpm. Results A total of 960 patients with ACS were included, 409 (43%) with ST-segment elevation myocardial infarction (STEMI) and 551 (57%) with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The C-ACS score predicted in-hospital mortality in all ACS patients with a C-statistic of 0.95 (95% CI: 0.93–0.96), in STEMI patients with a C-statistic of 0.92 (95% confidence interval [CI]: 0.89–0.94), and in NSTE-ACS patients with a C-statistic of 0.97 (95% CI: 0.95–0.98). Of the 960 patients, 218 (22.7%) were aged ≥75 years. The proportion of patients aged ≥75 years was 21.7% in the STEMI subgroup and 23.4% in the NSTE-ACS subgroup (P>0.05). Age ≥75 years was significantly associated with in-hospital mortality in ACS patients (odds ratio [OR]: 3.25, 95% CI: 1.24–8.25) and in the STEMI subgroup (OR >3.99, 95% CI: 1.28–12.44). Female sex was strongly associated with mortality in the NSTE-ACS subgroup (OR: 27.72, 95% CI: 1.83–39.99). Conclusion We conclude that C-ACS score was the strongest predictor of in-hospital mortality in all ACS patients while age ≥75 years predicted the mortality well in the STEMI subgroup.