Purpose <p>Psychosocial interventions have been designed for autism spectrum disorder (ASD), but most focus on youth. Adaptation to social context was examined before and after a pilot randomized control trial of a theatre-based intervention for autistic adults. Depressive symptom impact on treatment outcomes was also investigated.</p> Methods <p>Sixty-one adults, ages 18–40&#xa0;years with ASD, randomized to an experimental (EXP, <i>n</i> = 29) or waitlist control (WLC, <i>n</i> = 32) group, participated in a social interaction paradigm (Contextual Assessment of Social Skills; CASS) pre- and post-intervention. Depressive symptoms (Beck Depression Inventory) were examined as a predictor of behavioral change on the CASS post-intervention.</p> Results <p>Before the intervention, adults in the EXP and WLC group had significant behavior adaptation between the Interested and Bored CASS conditions (corrected <i>p</i> &lt; .01). Analysis of covariance of a Social Adaptation Index, controlling for pretest scores, was not significant for group (EXP vs WLC) (<i>F</i>(1,36) = 0.398, <i>p</i> = .532, η_p² = 0.011) or sex (<i>F</i>(1,36) = 0.160, <i>p</i> = .691, η_p² = 0.004). Depression and perception of peer behavior were correlated at pretest (<i>r</i> = -.277, <i>p</i> = .032), but pre-intervention depressive symptoms were not predictive of post-intervention behavior, nor was there a depression-by-group interaction (<i>p</i> &gt; .05).</p> Conclusions <p>The intervention did not significantly impact social adaptation as measured by behavioral changes across social interaction contexts; however, autistic adults were already able to differentiate social conditions prior to the intervention. The CASS may not be optimal for broadly measuring treatment effects in adults. Paradigms are needed to more comprehensively measure behaviors that may be enhanced following social skills interventions.</p> Trial Registration <p>The trial was pre-registered with ClinicalTrials.gov (Identifier: NCT04349644).</p>