To prospectively assess the clinical performance of a fluorescent optode-based blood gas monitoring system that is designed to perform arterial pH, PCO2, and PO2 measurements as frequently as clinically required without violating the integrity of the arterial catheter tubing system or permanently removing blood from the patient. A prospective, multicenter study to compare modern blood gas analyzer measurements with the coinciding measurements of the blood gas monitoring system. Four intensive care units (ICUs) in academic centers with varying patient populations, blood gas measurement routines, and blood gas laboratory facilities. Adult ICU patients (n = 117), with appropriately functioning radial arterial catheters in place, who were assessed as likely to require multiple arterial blood gas measurements for > or = 2 days. None. A total of 117 patients had 1,341 concurrent blood gas analyzer and monitor measurements of arterial pH, PCO2, and PO2 over a 1- to 4-day period. The range of values were 7.14 to 7.64 for arterial pH, 19 to 98 torr (2.5 to 13.0 kPa) for PaCO2, and 38 to 413 torr (5.1 to 54.9 kPa) for PaO2. Linear regression analysis of the optode-based monitor compared with the electrode-based blood gas analyzer demonstrated r2 values of .85 for pH, .92 for PCO2, and .94 for PO2. Comparative statistical analyses for bias (mean difference between analyzer and monitor) and precision (standard deviation of the mean difference [+/- SD] between analyzer and monitor) were respectively:-0.004 and +/- 0.027 for pH; -0.8 torr (-0.11 kPa) and +/- 2.4 torr (0.32 kPa) for PCO2; -2.2 torr (-0.31 kPa) and +/- 8.7 torr (1.2 kPa) for PO2. Clinical performance of this fluorescent, optode-based blood gas monitoring system demonstrates stability, consistency, and accuracy comparable to modern blood gas analyzers. This system withstood the normal abuse and rigors of clinical conditions common to the ICU while reliably performing in critically ill patients for up to 80 hrs. Use of the device did not significantly alter the function or longevity normally expected from a 20-gauge radial artery catheter. We submit that this blood gas monitoring system can replace the use of blood gas analyzers for ICU patients with indwelling arterial catheters.