Background: Medical device-associated infections (MDAIs) are a major healthcare concern due to their high morbidity, mortality, and rising prevalence of MDR and XDR bacteria. This study examined the microbiological composition, antimicrobial susceptibility, and prevalence of MDR/XDR infections in MDAI patients at Dr. D.Y. Patil Medical College, Pune. Methods: One-year retrospective research included 100 MDAI patients. Antimicrobial susceptibility testing was done on microbial isolates from blood, urine, and wound swabs according to CLSI standards. The prevalence of MDR and XDR pathogens was determined. Results: Escherichia coli (30%) and Klebsiella pneumoniae (20%) caused most infections, while Staphylococcus aureus (25%) was the most common Gram-positive bacteria. Antimicrobial susceptibility testing showed that 40% of the isolates were MDR and 15% were XDR. Klebsiella pneumoniae had the highest resistance rate (70%), followed by Pseudomonas aeruginosa. Conclusion: The study shows that MDAIs are dominated by MDR and XDR infections, mainly Gram-negative bacteria, making therapy difficult. These findings highlight the critical need for improved infection control, antimicrobial stewardship, and regular surveillance to address medical device-associated resistance infections. Keywords: Medical device infections, multidrug-resistant, extensively drug-resistant organisms, antimicrobial susceptibility, microbiological profile, healthcare-associated infections.