Background: Emerging evidence suggests that the APOE4 allele may increase the risk of a negative outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), but the results are conflicting. A genetic variable predicting the individual clinical course is currently lacking. Objective: To examine the association between the APOE4 allele and a negative outcome. A secondary objective was to investigate the association between the APOE4 allele and delayed ischemia, a major complication of SAH. Methods: We searched MEDLINE, EMBASE, the Cochrane Library, CINHAL, LILACS, and www.google.it through March 2006. We hand-searched journals, international conference proceedings, and reference lists of retrieved articles. Individual patient data were requested from the corresponding authors of the original articles. Information on study design, participant characteristics, clinical outcome, delayed ischemia, and confounder distribution were independently abstracted by two investigators. Results: We included eight observational studies (696 patients for the clinical outcome and 600 for the delayed ischemia analyses). The corresponding authors of all the retrieved publications but one gave their original data. Summary odds ratios (ORs) were calculated by means of the random-effect model. The risk of a negative outcome (OR = 2.558; 95% CI 1.610 to 4.065) and delayed ischemia (OR = 2.044; 95% CI 1.269 to 3.291) were increased in the E4 carriers. Conclusions: In patients with subarachnoid hemorrhage, the expression of the E4 allele is associated with a higher risk of a negative outcome and delayed ischemia.