Objective: Randomized clinical trials have reported low risks of bleeding in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients receiving triple antithrombotic treatment (aspirin, clopidogrel and heparin). As trial patients often differ substantially from unselected patients treated in routine clinical settings, we compared the incidence of bleeding in ‘real-life patients’ with the incidence in the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial. Methods: We conducted a historical follow-up study based on 195 nonselected patients diagnosed with NSTE-ACS admitted to a Danish hospital. Data were obtained through systematic review of medical records . Bleeding complications were registered for 6 months after the event. Results: One hundred and nineteen (61.0%) patients fulfilled the inclusion and exclusion criteria of the CURE trial and were treated with triple antithrombotic therapy. Eleven (9.2%) of the 119 patients suffered a life-threatening bleeding. Their relative risk of life-threatening bleeding was 4.3 (95% CI 2.4–7.7) compared with the CURE study population. There was no difference in minor bleeding. Among patients not eligible according to the CURE criteria, but receiving intensive antithrombotic treatment, the relative risk of life-threatening bleeding was 6.4 (95% CI 3.1–12.9). Conclusions: When triple antithrombotic therapy is used in clinical practice in NSTE-ACS patients, the risk of bleeding may exceed that reported in trials. Assessment of the bleeding risk in the individual patient is warranted.