Background: Antibiotic resistance poses a formidable challenge to global healthcare, with Gram-negative bacteria emerging as a primary concern. Multidrug-resistant Gram-negative bacilli (MDR-GNB) have become a significant cause of nosocomial infections, particularly pneumonia, complicate therapy, and have a detrimental impact on patients’ outcomes. Objectives: This study aims to investigate the etiology, risk factors, and antibiotic resistance patterns associated with Gram-negative bacilli (GNB) isolated from nosocomial pneumonia cases. Methods: This prospective cross-sectional study was conducted at the Microbiology laboratory of Smt. B.K. Shah Medical Institute and Research Center, Dhiraj Hospital, Piparia, Gujarat. The study was initiated after the ethical approval. Patient demographic and clinical details were noted in the preformed questionnaire. Sputum and Endotracheal aspirate (ET) samples were cultured on MacConkey’s agar and Blood agar and further species identification with Antimicrobial Susceptibility Pattern was done by automated Vitek-2 compact system. Results: Ventilator-associated Pneumonia (VAP) rate was found in 14.6% of infected patients, with male predominance and common in the 30-50 years age group. Out of them, 72% were mainly associated with late-onset. Overall, the major isolates were Pseudomonas aeruginosa (20/64, 31%), followed by Acinetobacter baumanni (19/64, 29.6%) and Klebsiella pneumoniae (17/64, 26.5%) both as solitary and mixed infections.76% strains of Klebsiella and 85% of E. coli strains were resistant to carbapenems and 93.3% of Acinetobacter baumannii were resistant to cephalosporins and carbapenems. Enterobacter cloaca strains were 100% resistant to carbapenems and Pseudomonas aeruginosa was 100% resistance to Tigecycline. Conclusion: The study recommends effective Infection control practices and strong antibiotic stewardship programs to reduce the morbidity and mortality of nosocomial pneumonia.