Critically ill patients often have cardiopulmonary perturbations that require rapid and frequent assessment for optimal care, including cardiac output determinations, measurement of cardiac filling pressures, and arterial and mixed venous blood gas determinations. We evaluated the performance of a rapid, on-demand bedside blood gas monitor to determine arterial and mixed venous blood gas values. The blood gas monitor uses fluorescent optode technology to directly measure Po2, Pco2, and pH. This measurement is accomplished by aspirating blood from the artery or vein into a sampling chamber where it interfaces with the fluorescent optode. After approximately 90 s of equilibration, the blood gas values are reported. Since the blood is drawn into the sampling chamber, it can be returned to the patient, thus eliminating the need for phlebotomy. We studied 15 critically ill patients requiring systemic and pulmonary arterial catheterization. Conventional blood gas analysis was performed simultaneously. The results obtained from the blood gas monitor were compared with those obtained via traditional blood gas analysis using Bland-Altman plots and examination of bias and precision. The results were well within the expected clinical variance. During the study period, there was no interference with patient care or adverse events related to the use of the monitoring system. In conclusion, the blood gas monitor can provide rapid, accurate determinations of arterial and mixed venous blood gases allowing optimal therapeutic interventions in critically ill patients.