This study evaluated the performance of the DiaSorin NxTAG GPP multiplex PCR system, the advanced successor of the Luminex-xTAG-GPP, in comparison to classical diagnostic techniques for stool samples. In a testing phase, we investigated 505 specimens using both the DiaSorin system and our conventional approach consisting of culture techniques, PCR detection and microscopic analysis. The multiplex PCR system proved to be superior in sensitivity, time efficiency, and pathogen range. The analysis of 2,462 stool samples after the system's implementation into routine diagnostics further confirmed its effectiveness. However, we encountered several Salmonella-positive samples, which could neither be confirmed by culture techniques nor by an independently performed Salmonella-specific PCR. This let us to permanently incorporate a confirmatory PCR assay for Salmonella-positive samples, in order to avoid false positives. Our findings indicate that the DiaSorin NxTAG GPP is a reliable and efficient diagnostic tool for most gastrointestinal pathogens, with the exception of Salmonella.