Background: Despite the widespread use of the Progressive Supranuclear Palsy Rating Scale (PSPRS), it is not known what change in this scale is meaningful for patients. Methods: We analyzed data from a large clinical trial in PSP-Richardson's syndrome (AL-108-231) to calculate minimal clinically important worsening. This was defined as the difference in mean change of PSPRS in subjects rated “a little worse” and those rated “unchanged” on the Clinicians' Global Impression of Change Scale. A multivariate analysis using logistic regression assessed the relationship between clinical worsening, PSPRS, depression, and activities of daily living. Results: The minimal clinically important worsening on the PSPRS was 5.7 points, corresponding to the mean decline over 6 months in the trial. Changes in activities of daily living and PSPRS were significantly associated with clinical worsening. Conclusions: Clinically meaningful change is measurable on the PSPRS over 6 months. © 2016 International Parkinson and Movement Disorder Society.