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A safety-orientated system of delivering parenteral anaesthetic drugs was assessed in a prospective incident monitoring study at two hospitals. Anaesthetists completed an incident form for every anaesthetic, indicating if an incident occurred. Case mix data were collected and the number of drug administrations made during procedures estimated. From February 1998 at Hospital A and from June 1999 at Hospital B, until November 2003, 74 478 anaesthetics were included, for which 59 273 incident forms were returned (a 79.6% response rate). Fewer parenteral drug errors occurred with the new system than with conventional methods (58 errors in an estimated 183 852 drug administrations (0.032%, 95% CI 0.024–0.041%) vs 268 in 550 105 (0.049%, 95% CI 0.043–0.055%) respectively, p = 0.002), a relative reduction of 35% (difference 0.017%, 95% CI 0.006–0.028%). No major adverse outcomes from these errors were reported with the new system while 11 (0.002%) were reported with conventional methods (p = 0.055). We conclude that targeted system re-design can reduce medical error.