The COVID-19 pandemic changed the nature of clinical research assessments. Little is known about the impact of face mask use on research assessments for autism spectrum disorder (ASD). This study reports on tolerability of face mask use, child characteristics associated with tolerability, and the impact of face mask use on researcher ASD diagnostic certainty ratings. This paper describes results from a larger study of children who were clinically diagnosed with ASD in early childhood and were re-evaluated at age 5–7 years. Research diagnostic evaluations were conducted from 2018 to 2022 and included cognitive, language, and social-communication assessment. A research psychologist completed a rating scale on the potential impact of face mask use on research assessment diagnostic certainty for a subset of participants (n = 60) who were evaluated during the COVID-19 pandemic. The mean age of study participants was 6.2 years. Face masks were tolerated throughout the assessment for 40 children (66.7%); part-time for 13 (21.6%); and not tolerated for 7 (11.6%). Analysis of Variance (ANOVA) suggested that children who did not tolerate a face mask had significantly lower cognitive [F(2, 59) = 13.241, p < 0.001] and communication [F(2, 59) = 13.639, p < 0.001] scores compared to children who wore their mask for all or part of the visit. For 88% of research assessments, research staff indicated that face mask use had “no impact” on overall assessment results. Face mask use during clinical research assessment was not reported by research staff to significantly impact their ability to complete ASD evaluations.