The current analysis reexamines the relationship between supplemental vitamin E and all-cause mortality. All randomized, controlled trials testing the treatment effect of vitamin E supplementation in adults for at least one year were sought. MEDLINE, the Cochrane Library, and Biological Abstracts databases were searched using the terms "vitamin E," "alpha-tocopherol," "antioxidants," "clinical trial," and "controlled trial" for studies published through April 2010; results were limited to English, German, or Spanish language articles. Studies were also obtained through reference mining. All randomized controlled trials using vitamin E, with a supplementation period of at least one year, to prevent or treat disease in adults were identified and abstracted independently by two raters. Mortality data from trials with a supplementation period of at least one year were pooled. The selected trials (n = 57) were published between 1988 and 2009. Sample sizes range from 28 to 39,876 (median = 423), yielding 246,371 subjects and 29,295 all-cause deaths. Duration of supplementation for the 57 trials range from one to 10.1 years (median = 2.6 years). A random effects meta-analysis produce an overall risk ratio of 1.00 (95% confidence interval: 0.98, 1.02); additional analyses suggest no relationship between dose and risk of mortality. Based on the present meta-analysis, supplementation with vitamin E appears to have no effect on all-cause mortality at doses up to 5,500 IU/d.