Conventional low biocompatibility peritoneal dialysis (PD) fluid composition has been driven by manufacturing expediency and cost limitations. PD is associated with significant acute changes in cardiovascular functional parameters, at least in part influenced by fluid composition. Short-term control of blood pressure (BP) is under control of the baroreflex arc. The aim of this study was to investigate the effects of PD fluid biocompatibility on baroreflex sensitivity (BRS). We studied 10 non-diabetic established continuous ambulatory PD patients, in a randomized crossover trial comparing conventional and biocompatible PD fluids. Systemic hemodynamics were continuously monitored using digital pulse-wave analysis. Plasma glucose and insulin were assessed during treatment with both 1.36% and 3.86% glucose-containing fluids. BRS was calculated offline from continuous BP and interbeat interval data. BRS was significantly higher with conventional PD fluid during both 1.36% (P<0.001) and 3.86% (P<0.001) dwells. Systolic BP was higher; heart rate, stroke volume, and cardiac output were lower; and total peripheral resistance increased during exposure to either fluid. There were significant differences between fluids with respect to the magnitude of these responses. Plasma glucose and insulin concentrations, and ultrafiltration volumes were significantly higher during the 3.86% dwell than the 1.36% dwell, but there were no differences between standard and biocompatible fluids. We have demonstrated for the first time that PD fluid biocompatibility rapidly affects BRS. These changes occur against a background of cardiovascular variability, hyperinsulinemia, and hyperglycemia. Further research is needed to explore the mechanism and, more importantly, the consequences of these findings.