Background: Ischaemic stroke (IS) is a complex disease that involves genetic and environmental factors. The role of factor XI (FXI) in arterial thrombosis is unclear. We have investigated the risk of IS related to FXI levels in a case-control study. Methods: We studied 445 individuals: 218 diagnosed with IS and 227 age-gender-ethnic matched control subjects. We measured factor VIIIc, fibrinogen and factor XIc levels. FXI < 144% was taken as the reference group in the statistical analysis. Results: There were 104 women and 114 men in the IS group and 108 women and 119 men in the control group. The crude odds ratio (OR) of IS in dyslipidaemic patients with high levels of FXI was 4.2 [95% confidence interval (CI): 1.2-14.8] compared with dyslipidaemic controls and low levels of FXI, but the OR in the non-dyslipidaemic with high levels of FXI subgroup was 1.2 (95% CI: 0.4-3.2). The adjusted OR of IS in dyslipidaemic patients with high levels of FXI was 6.4 (95% CI: 1.6-26.1) compared with dyslipidaemic controls, but the OR in non-dyslipidaemic subgroup with high levels of FXI was 0.6 (95% CI: 0.2-2.1). Conclusion: We found almost a sixfold higher risk of IS in patients with dyslipidaemia and high levels of FXI. Further studies should elucidate the role of FXI in IS and therapeutic approaches should become apparent for patients with dyslipidaemia and high-FXI plasma levels. © 2007 The Authors.