Objective: Multidrug-resistant Gram-negative bacteria cause difficult-to-treat infections associated with high mortality. Carbapenems are widely used; however, their overuse has led to the emergence of carbapenem-resistant bacteria. This study aimed to evaluate the indications, clinical and microbiological efficacy, and side effects of ceftazidime-avibactam (CAZ-AVI) and to identify factors influencing mortality, based on data from a large multicenter patient cohort in Türkiye. Materials and Methods: Patients with carbapenem-resistant but CAZ-AVI-susceptible Gram-negative bacterial infections who received CAZ-AVI treatment were retrospectively reviewed. Results: A total of 1245 patients were included. The most common indication for CAZ-AVI use was hospital-acquired pneumonia (47.8%). Klebsiella pneumoniae was the predominant pathogen (81.3%). CAZ-AVI was used as a monotherapy in 80% of cases. Clinical side effects were observed in 8 (0.64%) patients, while laboratory abnormalities occurred in 73 (5.86%). The 7-day, 14-day, and 28-day all-cause mortality rates were 13.8%, 28.9%, and 45.2%, respectively. Microbiological eradication was achieved in 82.3% of patients. Higher Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores at admission, requirement for continuous renal replacement therapy, mechanical ventilation, and elevated C-reactive protein levels were identified as independent risk factors for mortality. Conclusion: This large multicenter real-world analysis demonstrates that CAZ-AVI is an effective treatment option for severe infections with high mortality, such as those caused by carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa.