BackgroundLower respiratory tract infections are the most common health problem, demanding frequent consultation and hospitalization. Moreover, there has been a dramatic rise in antibiotic resistance among respiratory pathogens. ObjectiveThis study aimed to assess the bacterial profile, antimicrobial susceptibility patterns, and associated factors of lower respiratory tract infection among patients attending at Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia, in 2023. MethodA hospital-based cross-sectional study was conducted on a total of 305 study participants from May 1 to July 30, 2023. Purulent sputum samples were collected and streaked onto chocolate agar, blood agar, and MacConkey agar. Chocolate agar and blood agar plates were incubated at 35-37 degrees C for 24 h with 5% carbon dioxide in a candle jar. MacConkey agar was incubated aerobically at 35-37 degrees C for 24 h. Antimicrobial susceptibility patterns were determined via the disk diffusion method (Kirby-Bauer) on Mueller-Hinton agar. A logistic regression model was used to show the relationship between the outcome and independent variables. ResultOf a total of 305 samples, 33.4% (95% CI: 29.2-38.8%) samples showed growth of various species of bacteria. The predominant pathogens were Klebsiella pneumoniae 31/102 (30.4%), Streptococcus pneumoniae 21/102 (20.6%), and Pseudomonas aeruginosa 16/102 (15.7%). The overall magnitude of multidrug resistance (MDR) was 47.1%. Having > 58 age groups (AOR = 7.180, 95% CI: 1.858-27.743), being illiterate (AOR = 2.76, 95 CI: 1.158-6.578), chronic cough (AOR = 5.26, 95% CI: 1.725-16.038), and alcohol drinking (AOR = 6.542, 95% CI: 2.570-16.654), were determinants of lower respiratory tract infection. ConclusionK. pneumoniae and S. pneumoniae were the most predominant pathogens. A high levels antibiotic resistance was present in the majority of the isolates. Therefore, antibiotic susceptibility testing should be applied to guide treatment decisions.