Multiple theoretical perspectives connect vagally mediated heart rate variability, or respiratory sinus arrhythmia (RSA), and self-regulatory and interpersonal processes. Together they suggest that self-regulatory effort and positive social experiences may lead to short-term increases in RSA, which in turn are related to adaptive emotional, social, and physical functioning. However, the extant literature on adult social interactions does not clearly support this premise. To study the connections between dyadic social interactions and phasic changes in RSA, the current research examined 356 dyads (712 adults between 18 and 36 years; 50% males, 50% females) across three studies in which participants engaged in face-to-face social interactions in a laboratory setting. Relationship type and conversation context varied across studies, and high-frequency power was used to estimate RSA across resting baseline, anticipatory periods, and conversation tasks. Analyses indicated that anticipation of and engagement in dyadic social interactions were associated with an increase in RSA from a resting baseline. The mean estimated effect size for anticipation was r = 0.50, and the mean estimated effect size for conversation was r = 0.34. Associations were robust across relationship types, including strangers and romantic couples, conversation context, including topic and valence, and across speaking and listening roles. The present research provides consistent evidence for increased RSA in anticipation of and during in-person social interactions among adults, prompting the need for further investigation into potential underlying mechanisms.