OBJECTIVES: Decreased susceptibility to vancomycin has led to recommendations for increased serum concentration targets for some infections, which has been shown to increase the risk of nephrotoxicity (NT).  The objective of this study was to determine if vancomycin-induced nephrotoxicity has a significant impact on cost from the hospital perspective or on length of stay METHODS: A cost of illness study from the hospital perspective.  We conducted a secondary analysis of a cohort of 398 randomly selected inpatients receiving vancomycin in a tertiary care hospital in Rochester, New York, USA.  Total and variable costs were generated by hospital accountants using micro-costing methods.  NT was defined as 0.5 or 50% or greater increase in serum creatinine from baseline.  Generalized linear models with log link and gamma distribution and semi-log regression were used to model total and variable costs and length of stay, respectively.  Cost estimates are reported in 2009 USD RESULTS: 49 (12%) of patients had NT.  The unadjusted median variable costs for patients with NT were higher than for patients without NT ($47,511 vs. $22,355, p<.0001).  On multivariable analysis, variable costs were 18% greater for patients with NT compared to patients without, but this difference was not statistically significant.  The median length of stay for patients with NT was two-fold greater than for patients without NT (22 vs. 11 days, unadjusted, p<.0001).  After accounting for severity of illness and other factors, NT patients stayed on average 46% longer than non-nephrotoxic patients CONCLUSIONS: Patients with NT have significantly increased length of stay relative to patients without NT.  Further research is needed to confirm whether increased length of stay has a meaningful impact on costs.  As vancomycin susceptibility continues to decrease, higher doses of vancomycin may lead to an increased incidence of NT and an increase in resource utilization among these patients