Glycopeptide-intermediate S. aureus (GISA), particularly heterogeneous GISA (hGISA), remain difficult to detect in the routine practice of medical microbiology. Novel tools have been evaluated comparatively to the population analysis profile-area under the curve (PAP-AUC) reference method for detecting GISA/hGISA. Among them, the Etest GRD showed relatively high specificity (85.8-97%) and negative predictive value (97%) but lower sensibility (57-95%) and positive predictive value (30.8%). We investigated the utility of the Etest GRD for detecting GISA/hGISA among 180 strains isolated from 106 cystic fibrosis (CF) patients. Etest GRD was performed on all isolates, and those exhibiting a GISA/hGISA phenotype were further tested by PAP-AUC and other agar routine assays for GISA/hGISA detection. The Etest GRD allowed the detection of 15 GISA/hGISA strains, of which eight were confirmed by the reference method. Despite the 3.9% level of false positive results, the Etest GRD constitutes a useful routine tool for detecting GISA/hGISA overlooked by other routine assays, two strains being detected by the Etest GRD only. GISA/hGISA represented 7.7% of MRSA and 2.1% of MSSA, and were found in 4.7% of CF patients colonized/infected by S. aureus, which is the highest rate reported to date in this population.