The FloTrac/Vigileo, introduced in 2005, uses arterial pressure waveform analysis to calculate cardiac output (CO) and stroke volume variation (SVV) without external calibration. The aim of this systematic review is to evaluate the performance of the system. Sixty-five full manuscripts on validation of CO measurements in humans, published in English, were retrieved; these included 2234 patients and 44 592 observations. Results have been analysed according to underlying patient conditions, that is, general critical illness and surgery as normodynamic conditions, cardiac and (post)cardiac surgery as hypodynamic conditions, and liver surgery and sepsis as hyperdynamic conditions, and subsequently released software versions. Eight studies compared SVV with other dynamic indices. CO, bias, precision, error, correlation, and concordance differed among underlying conditions, subsequent software versions, and their interactions, suggesting increasing accuracy and precision, particularly in hypo- and normodynamic conditions. The bias and the trending capacity remain dependent on (changes in) vascular tone with most recent software. The SVV only moderately agreed with other dynamic indices, although it was helpful in predicting fluid responsiveness in 85 of studies addressing this. Since its introduction, the performance of uncalibrated FloTrac/Vigileo has improved particularly in hypo- and normodynamic conditions. A error at or below 30 with most recent software allows sufficiently accurate and precise CO measurements and trending for routine clinical use in normo- and hypodynamic conditions, in the absence of large changes in vascular tone. The SVV may usefully supplement these measurements.