Most clinical practice guidelines recommend restrictive red blood cell (RBC) transfusion practices with the goal of minimizing transmission of blood-borne pathogens. The purpose of this review is to compare clinical outcomes in patients randomized to restrictive versus liberal transfusion thresholds (triggers). We conducted a search of OVID Medline, Current Contents, the Cochrane Library, and bibliographies of published studies. Our search strategies used a combination of key-word terms as text and MeSH headings relating to transfusion triggers. We included trials if the comparison groups were assigned on the basis of a clear transfusion trigger or threshold, and the study was randomized with a concurrent control group. Eligibility of studies was assessed by 2 independent raters, with disagreements resolved by consensus. Disagreements not resolved by consensus were referred to a third party for review. Two raters assessed the methodologic quality of the trials modified from the methods of Schultz. The main study outcomes probability of receiving an RBC transfusion, volume of RBCs transfused, hematocrit levels, mortality, and length of hospital stay. Ten trials, which reported outcomes for a total of 1,780 patients, were included. Five studies were in surgical patients, 3 were in the setting of acute blood loss and trauma, and 2 involved intensive care unit patients. Transfusion triggers varied between 7 and 10 g/dL (most often they were 8 or 9 g/dL). Being randomized to a restrictive transfusion trigger group had the following average effects: the probability of receiving an RBC transfusion was reduced by 42% (relative risk, 0.58; 95% confidence interval [CI] 0.47, 0.71), the volume of RBCs was reduced by 0.93 units (95% CI 0.36, 1.5 units), and hematocrit values were 5.6 % lower (95% CI 3.5, 7.7%). Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity, and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood, the data may constitute a stronger basis for avoiding transfusion with allogeneic RBCs.