Prior research has shown that nurse staffing is an important consideration with regard to patient safety. Lower nurse-to-patient ratios are associated with increased mortality and have prompted policies mandating particular nurse staffing ratios, especially in the intensive care unit. To address the criticism that previous studies have compared different institutions with higher nurse staffing to those with lower staffing levels and that there may be other reasons for observed differences in patient outcomes, this study evaluated the relationship between inpatient mortality and exposure to shifts with decreased registered nurse staffing, lower nursing support staffing, and increased patient turnover at three sites within a single academic medical center. Consistent with prior studies, researchers found an association between low nurse and nursing support staffing and increased patient mortality; there was no association between patient turnover and mortality. An accompanying editorial advocates for additional prospective research on interventions put in place to address nurse staffing.