Heart rate (HR) and arterial blood pressure (BP) changes have been reported during conscious sedation with propofol and midazolam. One potential mechanism to explain these changes is that propofol and midazolam affect HR and BP via changes in the cardiac autonomic nervous system. Two specific hypotheses were tested by HR variability analysis: 1) propofol induces predominance of parasympathetic activity, leading to decreased HR and BP, and 2) midazolam induces predominance of sympathetic activity, leading to increased HR and decreased BP. Thirty dental patients were included in a prospective, randomized study. HR, BP, low frequency (LF), high frequency (HF), and entropy were monitored during the awake, sedation, and recovery periods and depth of sedation was assessed using the Observer’s Assessment of Alertness/Sedation score. Propofol induced a significant decrease in total power (503 ± 209 ms2/Hz versus 162 ± 92 ms2/Hz) and LF/HF ratio (2.5 ± 1.2 versus 1.0 ± 0.4), despite the absence of any change in HR during the sedation period compared with baseline. Midazolam decreased normalized HF (34 ± 10% versus 10 ± 4%) but did not significantly change LF/HF ratio (2.3 ± 1.1 versus 2.2 ± 1.4) and increased HR in the sedation period. Compared with baseline, propofol was associated with a significant increase in normalized HF in the recovery period (34 ± 11% versus 44 ± 12%) and a significant decrease in HR, whereas midazolam was associated with an increase in LF/HF ratio (2.3 ± 1.1 versus 3.7 ± 1.8) with no change in HR. These results indicated a dominant parasympathetic effect of propofol and a dominant sympathetic effect of midazolam in both periods. These results should be considered during conscious sedation, especially in patients at risk of cardiovascular complications.