Objective: To assess the overall risk of stroke, specifically ischemic stroke, associated with tamoxifen use by performing a meta analysis of data reported in breast cancer trials. Background: Tamoxifen increases the ri sk of venous thromboembolism in women with breast cancer, but its relationship t o stroke risk is uncertain. Methods: A systematic review of randomized controlle d trials of tamoxifen for breast cancer management and prevention published sinc e 1980 was performed using MEDLINE. The summary odds ratio (OR) and 95%CI were calculated using the Mantel Haenszel method, followed by a statistical test for heterogeneity. Results: Nine trials met the inclusion criteria, and six trials specified ischemic stroke outcomes. The Mantel Haenszel summary OR was 1.82 (95 %CI, 1.41 to 2.36) for ischemic stroke and 1.40 (1.14 to 1.72) for any stroke. The χ2 heterogeneity test was 6.0 (p >0.1) for ischemic stroke and 16.1 (p < 0. 05) for any stroke. The random effects summary OR of Der Simonian and Laird for any stroke was 1.29 (0.92 to 1.81). During a mean follow up period of 4.9 year s, the frequency of ischemic stroke was 0.71%with tamoxifen vs 0.39%for contro ls (absolute increased risk, 0.32%; number needed to harm [NNH], 313). Conclu si ons: Women with breast cancer who were treated with tamoxifen had an 82%increas ed risk of ischemic stroke and a 29%increased risk of any stroke, but the absol ute risk is small. Further studies assessing prespecified cerebrovascular outcom es are ongoing and will further clarify the risk of stroke associated with tamox ifen use. Objective: To assess the overall risk of stroke, specifically ischemic stroke, associated with tamoxifen use by performing a meta-analysis of data reported in breast cancer trials. Background: Tamoxifen increases the ri sk of venous thromboembolism in women with breast cancer, but its relationship Methods: A systematic review of randomized controlle d trials of tamoxifen for breast cancer management and prevention published sinc e 1980 was performed using MEDLINE. The summary odds ratio (OR) and 95% CI were calculated using the Mantel Haenszel method, followed by a statistical test for heterogeneity. Results: Nine trials met the inclusion criteria, and six trials specified ischemic stroke outcomes. The Mantel Haenszel summary OR was 1.82 (95% CI, 1.41 to 2.36) for ischemic stroke and 1.40 The χ2 heterogeneity test was 6.0 (p> 0.1) for ischemic stroke and 16.1 (p <0.05) for any stroke. The random effects summary OR of Der Si monian and Laird for any stroke was 1.29 (0.92 to 1.81). During a mean follow up period of 4.9 years, the frequency of ischemic stroke was 0.71% with tamoxifen vs 0.39% for contro ls (absolute increased risk, 0.32%; number needed to harm [NNH], 313). Conclu si ons: Women with breast cancer who were treated with tamoxifen had an 82% increas ed risk of ischemic stroke and a 29% increased risk of any stroke, but the absol ute risk is small Further studies assessing prespecified cerebrovascular outcom es are ongoing and will further clarify the risk of stroke associated with tamox ifen use.