BACKGROUND: Blood for transfusion is stored for up to 42 days. Older blood develops lesions and accumulates potentially injurious substances. Some studies report increasing toxicity as blood ages. We assessed the safety of transfused older versus newer stored blood. STUDY DESIGN AND METHODS: PubMed, Scopus, and Embase were searched using terms new and old and red blood cell and storage through May 6, 2011, for observational and randomized controlled studies comparing outcomes using transfused blood having longer and shorter storage times. Death was the outcome of interest. RESULTS: Twenty‐one studies were identified, predominantly in cardiac surgery (n = 6) and trauma (n = 6) patients, including 409,966 patients. A test for heterogeneity of these studies' results was not significant for mortality (I2 = 3.7%, p = 0.41). Older blood was associated with a significantly increased risk of death (odds ratio, 1.16; 95% confidence interval CI, 1.07‐1.24). Using available mortality data, 97 (95% CI, 63‐199) patients need to be treated with only new blood to save one life. Subgroup analysis of these trials indicated that the increased risk was not restricted to a particular type of patient, size of trial, or amount of blood transfused. CONCLUSION: Based on available data, use of older stored blood is associated with a significantly increased risk of death.