BACKGROUND: Several new trials evaluating transfusion strategies in patients with cardiovascular disease have recently been published, increasing the number of enrolled patients by over 30%. The objective was to evaluate transfusion thresholds in patients with cardiovascular disease. METHODS: We conducted an updated systematic review of randomized trials that compared patients assigned to maintain a lower (restrictive transfusion strategy) or higher (liberal transfusion strategy) hemoglobin concentration. We focused on new trial data in patients with cardiovascular disease. The primary outcome was 30-day mortality. Specific subgroups were patients undergoing cardiac surgery and with acute myocardial infarction. RESULTS: A total of 37 trials that enrolled 19,049 patients were appraised. In cardiac surgery, mortality at 30days was comparable between groups (risk ratio 0.99; 95% confidence interval 0.74-1.33). In 2 small trials (n=154) in patients with myocardial infarction, the point estimate for the mortality risk ratio was 3.88 (95% CI, 0.83-18.13) favoring the liberal strategy. Overall, from 26 trials enrolling 15,681 patients, 30-day mortality was not different between restrictive and liberal transfusion strategies (risk ratio 1.0, 95% CI, 0.86-1.16). Overall and in the cardiovascular disease subgroup, there were no significant differences observed across a range of secondary outcomes. CONCLUSIONS: New trials in patients undergoing cardiac surgery establish that a restrictive transfusion strategy of 7 to 8g/dL is safe and decreased red cell use by 24%. Further research is needed to define the optimal transfusion threshold in patients with acute myocardial infarction.