© 2020 International Parkinson and Movement Disorder Society Introduction: Statins were proposed to be neuroprotective; however, the effects are unknown in progressive supranuclear palsy (PSP), a pure tauopathy. Methods: Data of 284 PSP cases and 284 age-matched, sex-matched, and race-matched controls were obtained from the environmental and genetic PSP (ENGENE-PSP) study. Cases were evaluated with the PSP Rating Scale, Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, and Neuropsychiatric Inventory. Statin associations with PSP risk, onset age, and disease features were analyzed. Results: Univariate models showed lower PSP risk for type 1 statin users (simvastatin, lovastatin, pravastatin). After adjusting for confounding variables, statin use and lower PSP risk association remained only at a trend level. For PSP cases, type 1 statins were associated with 1-year older onset age; type 2 statins (atorvastatin, rosuvastatin) were associated with the lower PSP Rating Scale and Unified Parkinson's Disease Rating Scale. Conclusion: Statins may have inverse associations with PSP risk and motor impairment. Randomized prospective studies are required to confirm this effect. © 2020 International Parkinson and Movement Disorder Society.