INTRODUCTION: Cardiac autonomic dysregulation has been proposed in panic disorder (PD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed. METHODS: Forty-eight drug-naive individuals with PD and 202 healthy volunteers were recruited for a case-control analysis. We used the Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory to assess anxiety severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire. RESULTS: Patients exhibited reduced mean RR interval (816.94 +/- 135.92 versus 873.47 +/- 143.36 ms, P = 0.014) and HRV levels (Var 6.37 +/- 1.32 versus 7.38 +/- 0.95, LF 4.90 +/- 1.63 versus5.82 +/- 1.11 and HF 4.57 +/- 1.53 versus 5.62 +/- 1.24 [ln(ms2)], all P < 0.001) as compared to controls, which mainly suggested a reduction in cardiac vagal control in PD. The anxiety severity was negatively correlated with HRV levels (r = -0.29 for Var, r = -0.22 for LF and r = -0.28 for HF, all P < 0.001). The harm avoidance score (which has been suggested to be associated with serotonergic activity) was associated with decreased HRV levels (r = -0.22 for Var, P < 0.01, r = -0.14 for LF, P < 0.05 and r = -0.17 for HF, P < 0.01). DISCUSSION: This study demonstrates that PD is associated with cardiac autonomic dysregulation, highlighting the importance of assessing HRV in PD patients.