Background: The non-diphtherial Corynebacteria, also called ³CRU\QefRUmV´ bacWeUia are a diversified group of gram positive non sporing bacilli belonging to the genus Corynebacteria. Such bacteria are considered members of human microbiota (skin, respiratory and genital mucus membranes). Coryneform bacteria's pathogenic capacity has been undervalued until recently. Despite of frequently deemed as contaminants, these bacteria have been correlated to diverse clinical infections recently. Objectives: To isolate, speciate, and determine antimicrobial susceptibility pattern of clinically relevant non-diphtherial Corynebacteria from various clinical samples. Methodology: Different clinical samples (blood, urine, sputum, wound swabs, pus) collected from hospitalized patients attending at Zagazig University Hospital. The samples were processed and cultured as per conventional bacteriological methods. A total of 75 clinically relevant corynebacterial isolates exhibited speciation utilizing matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis and their antibiogram was done by disc diffusion method by means of combined guidelines of Clinical and Laboratory Standards Institute (CLSI) as well as British Society for Antimicrobial Chemotherapy (BSAC) because of lack of definite CLSI guidelines. Results: The mean age of the studied patients was 64.6 ± 14.9 years, 60% were male and 40% female. A total 75 clinically relevant Corynebacteria species were obtained from different clinical samples, including wound swabs and pus (53%), sputum (20%), and blood (17%). Forty two percent were isolated from ICUs. The most prevalent isolated species was C.amycolatum (27%), C. striatum (20%), and C.jeikieum (16%). Beta lactam antibiotics showed least activity against Corynebacteria species with resistance rate against penicillin 76% and ceftriaxone 72%, while all isolates exhibited uniform sensitivity (100%) against vancomycin as well as linezolid. Conclusion: This study showed isolation of different clinically relevant non-diaphterial Corynebacteria from different clinical samples with pus and wound swabs as the most common samples from which Corynebacteria were isolated. In particular, C.amycolatum was the most common isolated species. Beta lactam antibiotics (penicillin, ceftriaxone) showed the least activity while vancomycin and linezolid were the most active agents against nondiapdhterial Corynebacteria isolates. Herein, we confirm diphtheroids¶ clinical importance among different infections that necessitate evaluating their susceptibility patterns to some common antibacterial agents for guide the best antibiotic to treat