Background Metabolic and mechanical stress in the failing heart activates the cardiac sympathetic afferent reflex (CSAR). It has been demonstrated that cardiac resynchronization therapy (CRT) acutely reduces muscle sympathetic nerve activity in clinical responders. Mechanistically, this beneficial effect might be explained by acute deactivation of the CSAR. In addition to sympathoexcitation, CSAR inhibits the arterial baroreflex at the level of the nucleus tractus solitarii. Hence, in responders, CRT is likely to remove/reduce this inhibition. Therefore, we hypothesized that CRT acutely facilitates the arterial baroreflex. Methods and Results One day after implantation of a CRT device in 32 patients with chronic heart failure (LVEF, 27± 6%) we measured noninvasive baroreflex sensitivity (BRS) and heart rate variability (HRV) in two conditions: CRT device switched-on and switched-off (on/off order randomized). BRS changes were correlated with the difference in unpaced/paced LVEF, a measure of acute mechanical response to CRT. CRT increased BRS by 35% from 2.96 to 3.79 mmHg (P<0.02) and increased HRV (standard deviation of the intervals between normal beats) from 18.5 to 24.0 ms (P<0.01). The CRT induced relative change in BRS correlated with the change in LVEF (r=0.44, P<0.01). Conclusion CRT acutely increases BRS and HRV. This favourable response of the autonomic nervous system might be caused by CRT induced CSAR deactivation. Follow-up studies should verify the mechanism of the acute response and the possible predictive value of an acute positive BRS response.