<p>Disparities in outcomes have been reported in numerous neurologic diseases. Examining clinical decision-making patterns and behaviors can inform points of intervention to improve disease management and outcomes. This experimental vignette study sought to measure the effects of race (Black, White) and gender (female, male) on variation in clinical decision-making for remitting-relapsing multiple sclerosis (RRMS), primary progressive MS (PPMS), stroke, Parkinson disease, and epilepsy. A factorial survey study using five clinical vignettes was distributed to neurologists in the United States. Race and gender were randomly modified across all vignettes. Correct diagnoses for each vignette were the main outcome and additional outcomes included response time and planned next steps (as a proxy of certainty). 621 neurologists completed the study. Participants consistently diagnosed stroke correctly, independent of race/gender variant. However, we noted some variability for the other conditions. RRMS was correctly diagnosed among White female vignettes 89% of the time, compared to 81–82% for the other vignette types (<i>p</i> = 0.13). For PPMS vignettes, females were more likely to be correctly diagnosed than males, and White vignettes more likely to be correctly diagnosed than Black vignettes. We observed some variability in treatment initiation as the specified next step across vignettes, as well as response time. We found that diagnosis and certainty varied by race and gender. The extent to which frequency of correct diagnosis varied suggests uncertainty and reliance upon the epidemiologic knowledge base, particularly as the distribution of correct diagnoses corresponds with the evidence base.</p>