Background: The epidemiologic evidence of whether hypertension is associated with Progressive Supranuclear Palsy (PSP) is inconsistent. The ENGENE-PSP case-control study determined various PSP risk factors including whether hypertension preceded PSP onset. Methods: Incident PSP cases per NINDS-PSP criteria and age-, sex-, race- matched controls were recruited from similar North American geographic areas. All study participants were administered standardized interviews to obtain data on demographics, medical history and medications. Statistics: We used univariate and multivariate conditional logistic regression models to measure the associations between PSP and the following predictor variables: education level, hypertension, comorbid vascular conditions (diabetes mellitus and hyperlipidemia), and classes of anti-hypertensive medications using odds ratios and 95% confidence intervals. Results: There were significant associations seen between PSP and hypertension (OR: 1.569; 95% CI 1.129–2.181; p-value = 0.007), education level (OR: 0.733; 95% CI 0.637–0.843; p-value<0.001) and beta-blocker use (OR: 2.000; 95% CI 1.053–3.799; p-value = 0.034). However, in the multi-variate analysis hypertension (OR: 1.492; 95% CI 1.045–2.129; p-value = 0.027) and education level (OR: 0.730; 95% CI 0.633–0.841; p-value<0.001) were the only significant associations. Conclusion: These results suggest that there is a modest, yet significant association between hypertension and PSP. Further studies will be needed to better understand the pathophysiological basis for this finding.