ImportanceAutistic children have poorer oral health and greater oral care challenges, which are often associated with sensory overresponsivity, than neurotypical peers. It is important to identify innovative solutions enabling dentists to successfully perform standard clinic-based procedures for this population.ObjectiveTo determine whether a sensory-adapted dental environment (SADE) reduces physiological and behavioral distress in autistic children undergoing dental cleanings, compared with a regular dental environment (RDE).Design, Setting, and ParticipantsThis randomized crossover trial was conducted at a pediatric dentistry clinic in a large urban children’s hospital between May 2016 and April 2022. Coders were blinded to study condition for physiological but not behavioral measurements. Autistic children aged 6 to 12 years were identified and invited to participate. Interested families were enrolled consecutively; after confirmation of autism diagnosis, children were randomized. Analysis for this per-protocol study were conducted from April to October 2022.InterventionEach child underwent 1 RDE and 1 SADE dental cleaning, administered in randomized and counterbalanced order approximately 6 months apart. SADE included modified visual, auditory, and tactile stimuli.Main Outcomes and MeasuresThe primary outcome was physiological stress, assessed by electrodermal activity. The secondary outcome was behavioral distress measured from video recordings.ResultsAmong 452 families invited to participate, 220 children were enrolled, and 162 children (mean [SD] age, 9.16 [1.99] years; 136 [84.0%] male) with confirmed autism were randomized, with 83 children receiving RDE first and 80 children receiving SADE first. Most children (94 children [58.0%]) had moderate autism severity. Children had significantly lower physiological stress during dental care in SADE compared with RDE (mean difference in skin conductance level, −1.22 [95% CI, −2.17 to −0.27] μS), suggesting decreased sympathetic activity and increased relaxation during SADE dental care. No significant differences were found in nonspecific skin conductance responses (mean difference, −0.30 [95% CI, −0.86 to 0.25] per min). Video-coded frequency and duration of behavioral distress (but not questionnaire) measures were significantly lower in SADE vs RDE (Cohen d = −0.84 to −1.19). Physiological stress was associated with behavioral distress during the dental cleaning (eg, nonspecific skin conductance responses associated with the Frankl Scale: β = −0.29; 95% CI, −0.39 to −0.19); age, IQ, and expressive communication moderated the intervention’s success. No participants withdrew due to adverse effects.Conclusions and RelevanceIn this randomized crossover trial of autistic children, using SADE was safe and efficacious in decreasing physiological and behavioral distress during dental care. This is important because enhancing oral care is critical for autistic children; this intervention may also be beneficial for populations beyond autism.Trial RegistrationClinicalTrials.gov Identifier: NCT02430051