Intravenous (i.v.) vancomycin is increasingly used as outpatient parenteral antimicrobial therapy (OPAT). Despite the potential advantages of administration by continuous infusion (CI) compared with intermittent infusion (II), the relative nephrotoxicity of these two modes of delivery has not been well established. We compared the rate of nephrotoxicity of vancomycin given by CI and II. A retrospective cohort study of OPAT patients receiving i.v. vancomycin between January 2004 to June 2008 was performed. All patients had a normal baseline serum creatinine concentration. Propensity scoring analysis was used to adjust for risk factors of CI. The primary outcomes examined were the prevalence and rate of onset of nephrotoxicity. A total of 167 patients receiving vancomycin were identified, 112 by CI and 55 by II. The overall cumulative prevalence of nephrotoxicity was 15.6%. There were significant differences in baseline characteristics between the two groups. Matching based on propensity scores was undertaken, leaving 80 patients available for the analysis. Both in unadjusted and adjusted analyses, vancomycin CI was associated with a slower onset of nephrotoxicity but not a lower prevalence of nephrotoxicity. Both groups received a similar cumulative vancomycin dose. In adult OPAT patients with normal renal function, vancomycin CI was associated with a slower onset of nephrotoxicity.