Background: In March 2020, the onset of the COVID-19 pandemic in the United States introduced new concerns related to the treatment of multiple sclerosis (MS). Objectives: To assess the impact of COVID-19-related concerns on disease-modifying therapy (DMT) selection patterns for progressive MS. Methods: In July-August 2020, US neurologists contributed chart reviews for a retrospective, cross-sectional audit of DMT-treated patients diagnosed with secondary progressive (SPMS) or primary progressive (PPMS) MS (n=169 physicians; n=764 charts). Analyzed data include 277 patients prescribed a DMT between March and August. Results: Prescribing physicians considered at least one DMT an inappropriate option because of COVID-19 concerns, whether clinical or non-clinical, for 46% of PfMS patients (CP). CP patients were more likely to have had a negative COVID-19 test (30% vs. 20%) and to have discussed COVID-19 safety/risk related to their therapy (39% vs. 26%) compared to patients whose therapy selection was not impacted by COVID-19 concerns (NI). Cladribine (12%), alemtuzumab (11%), natalizumab (11%), and ocrelizumab (11%) were most frequently considered inappropriate options due to COVID-19. More CP than NI patients were prescribed teriflunomide (9% vs. 3%). Although nonsignificant, more CP patients were prescribed an S1P receptor modulator (22% vs. 14%) and fewer were prescribed ocrelizumab (27% vs. 37%). Drivers of therapy selection did not differ between groups, apart from managed care preference being more impactful among CP versus NI patients. At the subtype level, CP patients diagnosed with not active SPMS were more frequently prescribed teriflunomide (24% vs. 4%) and PPMS patients siponimod (11% vs. 0%). Among active SPMS patients, COVID-19-appropriate option, managed care preference, low monitoring burden, and appropriate in JCV seropositive patients were more influential therapy selection drivers for CP compared to NI patients. While not significant, tolerability and initiation ease appeared to play more of role for CP not active SPMS patients, while convenience was more impactful among CP PPMS patients. Conclusions: The COVID-19 pandemic has impacted treatment choice among MS patients, especially related to immunosuppressant and infusion DMTs. When COVID-19 restricted the range of viable options, patients were more likely to be prescribed oral DMTs. Pandemic-related practice operational cuts may have also played a role in greater prescribing of therapies with low payer requirement burden and low monitoring burden.