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Measuring the effect of the Needlestick Safety and Prevention Act (NSPA) is challenging. No agreement exists on a common denominator for calculating injury rates. Does it make a difference? How are the law and safety-engineered devices related? What is the effect on injuries and costs? This study examines those issues in assessing the impact of the legislation on hospital worker percutaneous injuries.Using a historic prospective design, we analyzed injury data from 85 hospitals. Injury rates were calculated per 100 full-time equivalents, 100 staffed beds, and 100 admissions each year from 1995 to 2005. We compared changes for each denominator. We measured the proportion of the injury rate attributed to safety-engineered devices. Finally, we estimated a national change in injuries and associated costs.For all denominators, a precipitous drop in injury rates of greater than one-third (P < .001) occurred in 2001, immediately following the legislation. The decrease was sustained through 2005. Concomitant with the decrease in rates, the proportion of injuries from safety-engineered devices nearly tripled (P < .001) across all denominators. We estimated annual reductions of more than 100,000 sharps injuries at a cost savings of $69–$415 million.While the data cannot demonstrate cause and effect, the evidence suggests a reduction in hospital worker injury rates related to the NSPA, regardless of denominator. It also suggests an association between the increase in safety-engineered devices and the reduction in overall injury rates. The decreases observed translate into significant reductions in injuries and associated costs.