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Few studies have compared nebulized and intravenous (IV) colistin for multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia. This study compared the nephrotoxicity and clinical outcomes for these two delivery routes.This study retrospectively compared 95 critically ill surgical patients who were diagnosed with Acinetobacter baumannii ventilator associated pneumonia and received colistin between March 2013 and January 2016.The most common diagnoses were brain hemorrhage (27.4%), traumatic brain injury (20%), traumatic thoracic injury (15.8%), and secondary peritonitis (11.6%). Compared to the IV group, the nebulizer group was significantly older (60.0 vs. 67.5 years, p = 0.010), had higher APACHE II scores (16.3 vs. 19.9, p = 0.001), and more frequently had diabetes mellitus (6.8% vs. 21.6%, p = 0.043). Nephrotoxicity was more common in the IV group (60.5% vs. 15.7%, p < 0.0001). Both groups had similar microbiological and clinical outcomes (p = 0.921 and p = 0.719, respectively). Patients with nephrotoxicity exhibited prolonged IV or nebulized colistin treatment and more frequent combination with vancomycin. Nephrotoxicity was independently associated with IV delivery (odds ratio: 8.48, 95% confidence interval: 2.95–24.39, p < 0.0001).Nebulized colistin may have less nephrotoxicity and provide similar clinical results, compared to IV colistin.Colistin can be used intravenously or as a nebulized mist for treating VAP.This study compared the toxicity and clinical outcomes of these two routes.IV colistin was an independent and significant risk factor for nephrotoxicity.Nebulized and IV colistin provided similar clinical and microbiological outcomes.Nebulized colistin may be useful for treating critically ill surgical patients.