Given the high oxygen consumption of motor neurons, we sought to assess the frequency and prognostic value of arterial hypertension (affecting brain's oxygen supply) in amyotrophic lateral sclerosis (ALS). We consecutively and prospectively included all ALS patients with regular medical follow-up and documented blood pressure measurements and monitored them until death. Vascular factors diagnosed prior to the onset of motor signs in ALS patients were compared with those in a stratified, age- and gender-matched case-control population. The severity of leukoaraiosis on magnetic resonance imaging (MRI) was blindly assessed. Post mortem examinations were performed when authorized. Compared with controls (n = 408), the 102 ALS patients were significantly more likely to display hypertension (41-57%) and current smoking (15-26%). The number of years of hypertension was associated with survival (HR = 1.04 (1.01-1.07)). In a multivariate analysis, leukoaraiosis severity (HR = 1.214 (1.096-1.344)), current smoking (HR = 1.766 (1.085-2.872)) and low vital capacity (HR = 2.422 (1.266-4.633)) remained independent predictors of survival. Post mortem examinations revealed a greater frequency of leukoaraiosis in ALS patients (p = 0.02). In conclusion, the effect of chronic hypertension on survival might be exerted through abnormal neural perfusion. The higher frequency of recent hypertension in ALS patients may be due to a compensatory increase in blood pressure in response to a lower oxygen supply.