Objective: Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements. Design: Prospective, experimental piglet study. Setting: Animal laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation. MEASUREMENTS AND MAIN Results: $Δ$cHbD and $Δ$ctHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in $Δ$cHbD and $Δ$ctHb. After injection of 0.5 mL/kg, the mean (sd) increase in $Δ$cHbD and $Δ$ctHb was 0.175 (0.213) $μ$mol/L and 0.122 (0.148) $μ$mol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) $μ$mol/L and -0.312 (0.266) $μ$mol/L. Injection of 1.0 mL/kg caused a mean increase in $Δ$cHbD and $Δ$ctHb of 0.237 (0.203) $μ$mol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) $μ$mol/L and -0.523 (0.335) $μ$mol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for $Δ$cHbD (p = .06), $Δ$ctHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection. ConclusionS: Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model. Copyright © 2010 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.