Background: Pilot research has suggested that D-cycloserine (DCS) enhances treatment outcomes for anxiety disorders when employed as an adjunct to exposure therapy (ET). The aim of this study was to determine whether 50 mg of DCS enhances ET for social anxiety disorder (SAD) according to a comprehensive set of symptom and life impairment measures. Methods: In a randomized double-blind placebo-controlled trial, we administered 50 mg of DCS or placebo in combination with ET to 56 participants who met primary diagnosis for SAD. Results: Participants administered DCS reported greater improvement on measures of symptom severity, dysfunctional cognitions, and life-impairment from SAD in comparison with placebo-treated participants. Effect sizes were mostly in the medium range. Results also indicated that the amount of adaptive learning about one's ability to give speeches in front of an audience interacted with DCS to enhance treatment outcome. Conclusions: This study shows that the administration of DCS before ET enhances treatment outcomes for SAD. Results also provide the first preliminary evidence to suggest that DCS moderates the relationship between a reduction in negative appraisals about one's speech performance and improvement in overall SAD symptoms.