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Intravenous colistin is used to treat resistant Gram-negative infections and is associated with nephrotoxicity. In overweight and obese adults, a paucity of data exists regarding the incidence and predictors of such toxicity. A retrospective nested case-control study was performed over 35 months for patients receiving intravenous colistin for >72 h with a body mass index (BMI) of >25 kg/m 2 . The objective was to investigate the incidence and predictors of nephrotoxicity. Severity of acute kidney injury was defined by RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Dosing and mortality were secondarily investigated. Forty-two patients met the inclusion criteria, and 20 (48%) developed nephrotoxicity. Patients with toxicity were in the risk (15%), injury (5%), and failure (80%) categories based on RIFLE criteria. A logistic regression model identified four predictors of colistin-associated nephrotoxicity: a BMI of >31. . Among all of the patients, dosing based on the actual body weight and excessive dosing due to the use of the actual body weight were frequent at 64% and 92%, respectively. The 30-day all-cause in-hospital mortality rate was 40% in the toxicity group and 14% in the nontoxicity group (P ‫؍‬ 0.14). Patients receiving intravenous colistin should be monitored for nephrotoxicity, especially when the BMI exceeds 31.5 kg/m 2 . Prospective, randomized, controlled trials are warranted to further examine nephrotoxicity incidence and predictors and appropriate dosing strategies in this population. Intravenous colistimethate sodium (CMS, colistin) is a polymyxin-type antimicrobial currently used to treat multidrug-resistant (MDR) Gram-negative infections caused by bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae (19). Although it was first used in the 1950s, CMS fell into disuse primarily due to significant associated nephrotoxicity (NTX), with incidence reports now ranging from 0% to 53.5% (8). Its unique history has been described in multiple reviews (8,18,21,24), and there is a notable lack of definitive recommendations regarding the most efficacious and least toxic way to administer CMS, including in overweight and obese patients (for whom the ideal body weight [IBW] is recommended by the package insert [13,28]). As the obesity epidemic continues within the United States, at a rate of Ͼ33% among adults (10), the questions of what the risk factors for NTX are and how clinicians should administer CMS to these patients remain critical.Limited data are available regarding NTX in overweight or obese patients receiving intravenous CMS. Following a thorough review of the literature, the only previously published evaluation of more than one overweight or obese individual receiving intravenous CMS included 10 obese patients (defined as those with an actual body weight [ABW] that is Ͼ140% of the IBW) (4). This analysis found that excessive CMS dosing was frequent and that use of the ABW to calculate doses was associated with a higher rate of N...