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Most studies of the relationship between nurse staffing and patient outcomes in hospitals have shown that worse patient outcomes are associated with lower registered nurse (RN) staffing. However, inconsistent results exist, possibly because of the use of a variety of nurse staffing and patient outcomes measures and because of statistical methods that employ static, instead of change, relationships.The aim of the study was to examine the relationship between changes in RN staffing and patient safety events in Florida hospitals from 1996 through 2004.Using 9 years of data from 124 Florida hospitals, latent growth curve models were used to assess the impact on patient safety of RN staffing changes in hospitals. Patient safety measures were 4 of the 20 provider-level patient safety indicators (PSIs) developed by the Agency for Healthcare Research and Quality. Two measures of RN staffing—RN full-time equivalents and RN per adjusted patient day—were analyzed.Changes in RN full-time equivalents were positively related to changes in RN per adjusted patient day. All PSIs were negatively and significantly related to one or both RN staffing measures. Failure to rescue had the strongest relationship to RN staffing. Models of change relationships between staffing and PSIs were more likely to show significant relationships than models using initial levels. Initial levels of RN staffing tended to be unrelated to initial levels of PSIs.A negative relationship between RN staffing and PSIs was strongly supported with failure to rescue and was weakly supported with decubitus ulcers, selected infections, and postoperative sepsis. The PSIs should be retested in an expanded change model study using multistate or national sample Healthcare Cost and Utilization Project data.