Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are significant contributors to morbidity and mortality, often necessitating antimicrobial therapy. This study aimed to identify the bacterial pathogens responsible for AECOPD and their antimicrobial susceptibility patterns in a tertiary care setting in Kathmandu, Nepal. A descriptive cross-sectional study was conducted from September 27 to December 26, 2023, at Shree Birendra Hospital. A total of 273 sputum samples from inpatients were analyzed. High-quality samples, determined by Gram staining, were cultured on Blood, Chocolate, and MacConkey agars. Bacterial isolates were identified using standard microbiological techniques, and their antibiotic susceptibility was tested using the Kirby-Bauer method per CLSI (2018) guidelines. Among 273 sputum samples, 42 (15.4%) showed bacterial growth. The predominant isolates included Acinetobacter spp. (44.7%), Pseudomonas aeruginosa (23.4%), Klebsiella pneumoniae (21.3%), Escherichia coli (8.5%), and Citrobacter freundii (2.1%). Females accounted for 57.9% of cases, with the highest positivity (15.9%) among them. The majority of bacterial isolates were from patients aged 56-70 years. Alarmingly, all Acinetobacter spp. isolates exhibited resistance to all tested antibiotics. Other pathogens demonstrated varying resistance, with multidrug resistance observed in 100% of isolates. Pseudomonas aeruginosa showed the highest sensitivity to Gentamycin (90.9%) and Meropenem (81.8%), while Escherichia coli and Citrobacter freundii were 100% sensitive to Amikacin. The findings reveal a high prevalence of multidrug-resistant bacterial pathogens in AECOPD patients, emphasizing the need for routine pathogen surveillance and antibiotic stewardship programs. Tailored antimicrobial therapy based on local resistance patterns is critical for effective management and preventing the escalation of resistance. Keywords: AECOPD, bacterial pathogens, antimicrobial susceptibility, multidrug resistance, tertiary care.