BACKGROUND A growing body of research links working conditions, such as staffing levels and work environment characteristics, with safety for both patients and workers in health care settings, including sharps injuries in hospital staff nurses. METHODS Surveys of 11,516 staff nurses from 188 Pennsylvania general acute care hospitals in 1999 were analyzed. Hospital work environments, measured using the Practice Environment Scales of the Nursing Work Index--Revised, and staffing were tested as predictors of experiencing at least one sharps injury in the preceding year, both before and after controlling for nurse risk factors, use of safety-engineered devices, and hospital structural characteristics. RESULTS Nurses with less than 5 years of experience, perioperative nurses, and those performing routine venipuncture for blood draws were more likely to be injured. Nurses working in hospitals with the most favorable working environments were one-third less likely to be injured. Staffing levels were not associated with sharps injuries. CONCLUSIONS Across a large state, nurses working in acute care hospitals with better practice environments had fewer sharps injuries. Work environment conditions and specialty- and setting-specific risk factors deserve continued attention in sharps injury research.