Measuring cardiac output (CO) is an integral part of the diagnostic and therapeutic strategy in critically ill patients. During the last decade, the single transpulmonary thermodilution (TPTD) technique was implemented in clinical practice. The purpose of this paper was to systematically review and critically assess the existing data concerning the reproducibility of CO measured using TPTD (COTPTD). A total of 16 studies were identified to potentially be included in our study because these studies had the required information that allowed for calculating the reproducibility of COTPTD measurements. 14 adult studies and 2 pediatric studies were analyzed. In total, 3432 averaged CO values in the adult population and 78 averaged CO values in the pediatric population were analyzed. The overall reproducibility of COTPTD measurements was 6.1 ± 2.0 % in the adult studies and 3.9 ± 2.9 % in the pediatric studies. An average of 3 boluses was necessary for obtaining a mean CO value. Achieving more than 3 boluses did not improve reproducibility; however, achieving less than 3 boluses significantly affects the reproducibility of this technique. The present results emphasize that TPTD is a highly reproducible technique for monitoring CO in critically ill patients, especially in the pediatric population. Our findings suggest that obtaining a mean of 3 measurements for determining CO values is recommended.