Background: Altered cardiac autonomic control has often been reported in depressed persons and might play an important role in the increased risk for cardiovascular disease (CVD). A negative association between cardiac autonomic control and depression might become specifically clinically relevant in persons 60 years or older as CVD risk increases with age. Methods: This study included data of 321 persons with a depressive disorder and 115 controls participating in the Netherlands Study of Depression in Older Persons (mean age = 70.3 years, 65.7% female). Respiratory sinus arrhythmia (RSA), heart rate (HR), and preejection period (PEP) weremeasured and compared between depressed persons and controls. In addition, the role of antidepressants and clinical characteristics (e.g., age of depression onset and comorbid anxiety) was examined. Results: Compared with controls, depressed persons had lower RSA (mean [standard error of the mean] = 23.5 [1.2] milliseconds versus 18.6 [0.7] milliseconds, p = .001, d = 0.373) and marginally higher HR (73.1 [1.1] beats/min versus 75.6 [0.6] beats/min, p = .065, d = 0.212), but comparable PEP (113.9 [2.1] milliseconds versus 112.0 [1.2] milliseconds, p = .45, d = 0.087), fully adjusted. Antidepressants strongly attenuated the associations between depression and HR and RSA. Antidepressant-naïve depressed persons had similar HR and RSA to controls, whereas users of antidepressants showed significantly lower RSA. In addition, tricyclic antidepressant users had higher HR (p < .001, d = 0.768) and shorter PEP (p = .014, d = 0.395) than did controls. Conclusions: Depression was not associated with cardiac autonomic control, but antidepressants were in this sample. All antidepressantswere associatedwith low cardiac parasympathetic control and specifically tricyclic antidepressants with high cardiac sympathetic control.