Introduction: A large body of evidence suggests that predisposition to suicide, an important public health problem, is mediated to a certain extent by neurobiological factors. The objective of this cross-sectional study was to compare the prevalence of white matter hyperintensities (WMH) in patients with major affective disorders with and without histories of suicide attempts. Methods: T2-weighted magnetic resonance images (MRI) of 65 psychiatric inpatients with major depressive disorder or bipolar disorder were rated for the presence of WMH. Diagnoses, presence or absence of suicide risk and substance abuse were determined by the Mini International Neuropsychiatric Interview (MINI). Medical charts were reviewed to ascertain history of suicide attempt and basic clinical variables. Fisher's Exact Tests and logistic regression modeling were used to test the association between WMH and suicidality. Suicidal patients and controls were not matched for demographic variables and exposure to some risk factors. Results: Bivariate analysis showed that the prevalence of WMH was significantly higher in subjects with past suicide attempts (Fisher's Exact Test, p = 0.01) and other clinical indicators of elevated suicide risk. Logistic regression analyses controlling for age, sex, and several clinical risk factors supported this finding (odds ratio = 4.7; 95% confidence interval: 1.4, 16.1). Conclusions: The increased prevalence of WMH in adults with major affective disorders and a history of suicide attempt, compared to similar patients without such a history, is consistent with previous findings in depressed children, youth and young adults. However, the association between WMH and suicidality holds true for both, depressed and bipolar patients. Our results suggest that WMH in patients with major affective disorders might be useful biological markers of suicidality. © 2007 Springer.