Background Blood gas analysis and blood lactate measurement have important roles in patient management. Point-of-care (POC) testing simplifies and provides rapid blood gas and lactate measurements. This study aimed to compare pH, pCO(2), pO(2), and lactate measurements between a POC device and a benchtop blood gas analyzer typically used in a hospital central laboratory, and to evaluate the inter-device variability of the POC device. Methods A cross-sectional study was conducted with a sample size of 100. Each sample was measured for pH, pCO(2), pO(2), and lactate using a Nova pHOx plus L benchtop blood gas analyzer in the central laboratory and an i-STAT handheld POC device. The results of both devices were compared using Pearson or Spearman correlation coefficients and Bland-Altman tests. Testing of the inter-device variability was done by using three different i-STAT devices, and the results were compared statistically. Results Strong correlations were observed for all test results. In Bland-Altman analysis, >= 95% of the results were within the limits of agreement, with the exception of lactate, which had only 93%. The results that were beyond the limits were primarily lactate levels >8 mmol/L. Biases between the benchtop analyzer and the i-STAT were not clinically significant, except pH. No significant inter-device variability was observed between the i-STAT analyzers. Conclusion This comparison study of pH, pCO(2), pO(2), and lactate measurements between Nova pHOx plus L and i-STAT analyzers showed good agreement. However, lactate measurement results >8 mmol/L on the i-STAT analyzer should be interpreted with caution.