Background:– Coagulase–negative Staphylococcus (CoNS) are increasing importance because of their role as pathogens in nosocomial infection certain clinical conditions and their marked resistance to antibiotics and antimicrobial susceptibility pattern. This study aimed to determine clinically significant CoNS and antimicrobial susceptibility patterns in a tertiary care hospital. Methods: All clinical samples were performed by using standard microbiological techniques eg. Isolation, Identification, and antimicrobial sensitivity testing. Antimicrobial susceptibility testing was performed by the modified Kirby Bauer method as per the CLSI guidelines. Results: A total of 86 (28.95%) CoNS were found to be clinically significant. The most common CoNS infection was abscesses and wound infections (31.39%) followed by urinary tract infection (24.42%) and sputum (15.12%). The most Sensitive drug in CoNS was found to be Linezolid and Vancomycin (100%), followed by Clindamycin (80.23%). The most resistance Penicillin G (82.56%), Cefotaxime (63.95%), and Ciprofloxacin (56.98%). Conclusions: The role of CoNS as a pathogen, especially nosocomial and opportunistic is increasing. The antimicrobial susceptibility of CoNS is extremely eligible to permit a more precise determination of host–pathogen relationship and observation of pathogenicity.