To determine the impact of a multifocused interventional program on sharps injury rates. Sharps injury data were collected prospectively over a 9-year period (1990-1998). Pre- and postinterventional rates were compared after the implementation of sharps injury prevention interventions, which consisted of administrative, work-practice, and engineering controls (ie, the introduction of an anti-needlestick intravenous catheter and a new sharps disposal system). Sharps injury data were collected from healthcare workers employed by a mid-sized, acute-care community hospital. Preinterventional annual sharps injury incidence rates decreased significantly from 82 sharps injuries/1,000 worked full-time-equivalent employees (WFTE) to 24 sharps injuries/1,000 WFTE employees postintervention (P<.0001), representing a 70% decline in incidence rate overall. Over the course of the study, the incidence rate for sharps injuries related to intravenous lines declined by 93%, hollow-bore needlesticks decreased by 75%, and non-hollow-bore injuries decreased by 25%. The implementation of a multifocused interventional program led to a significant and sustained decrease in the overall rate of sharps injuries in hospital-based healthcare workers.