We examined respiratory sinus arrhythmia (RSA), emotion regulation (ER), and prospective depressive symptoms in children at risk for depression and controls. Of the 65 children (35 boys; 5-13 years) in the sample, 39 had a parent with childhood-onset mood disorder and 26 had a parent with no history of major psychiatric disorder. RSA during pre- and post-film baselines and RSA reactivity to sad film clip were measured. Later, children's ER responses (focusing on sad/distressing affect) were assessed using a parent-reported questionnaire, and depressive symptoms were measured via clinical ratings. Results indicated that, compared to the initial baseline, a greater decrease in RSA (i.e., more vagal withdrawal) in response to the sad film clip predicted more adaptive ER responses and lower levels of clinician-rated depressive symptoms. However, tests for ER as a mediator of the association between RSA reactivity and depressive symptoms were precluded because maladaptive, but not adaptive, ER was associated with depressive symptoms. Overall, results suggest that cardiac vagal withdrawal (a greater decrease in RSA) in response to an emotional stimulus reflects more adaptive parasympathetic activity, which could facilitate children's ability to effectively manage their sadness and distress and predict lower risk of depressive symptoms over time.