The objective of the present study was to investigate the diagnostic validity of a new diagrammatic approach to the diagnosis of acid-base balance disorders as proposed by A. Grogono. In order to examine the diagnostic validity of the proposed diagram, 3,122 arterial blood gas samples were drawn from 114 ICU patients and were interpreted using the Grogono diagram and the following approaches as comparators: 1. Τhe Siggaard-Andersen (S-A) chart, 2. The “Oxygen Status Algorithm” (OSA) software and 3. Τwo physicians with more than 10 years of experience in ICU, considered experts in acid-base balance disorders. Our results showed that: 1. Τhe Grogono diagram presents the higher diagnostic agreement with the other methods ranging from 59.7% to 72.5%; 2. The diagnostic agreement between the Grogono diagram and the OSA software (70.5%) is significantly higher (p<0.001) in comparison to that between the Grogono diagram and the S-A chart (59.7%); 3. Τhe ratios of diagnostic agreement between the Grogono diagram and each one of the two experts (72.5% and 62.1%, respectively) are significantly higher (p<0.001) than those calculated for the “S-A chart” (48.3% and 56.4%, respectively); 4. Τhe two expert physicians disagreed with each other in the diagnosis of 1/3 of the cases of arterial blood gases disturbances. Moreover, they presented significant diagnostic variation in the comparisons with the other methods. In conclusion, the Grogono diagram, although superior to the S-A chart, cannot be safely used for the diagnosis of acid-base balance disorders in everyday clinical practice, because it has been shown to provide inaccurate diagnoses in at least 25% of the cases. Pneumon 2004, 17(2):150-158.