Persistent Staphylococcus aureus bacteremia (SAB) has been documented throughout the literature, with rates of approximately 5-20%. Limitations of these reports include inconsistent definitions, lack of consideration for appropriate therapy, and small patient populations. Patients who developed SAB between July 1^st, 2008 and June 30^th, 2011 were examined in a retrospective cohort analysis to compare persistent (≥ 48 hours of active therapy) SAB to non-persistent (< 48 hours of active therapy) SAB. 366 cases of SAB were identified over the 3-year study period. 39 cases were persistent by definition (10.7%). Both severe renal impairment and renal replacement therapy were significantly associated with persistent SAB. The presence of osteomyelitis or central venous access device was significantly associated with persistent SAB. Median length of hospital stay was 18 days in the persistent group and 11 days in the non-persistent group (p = 0.0082). Mortality rate during hospitalization was not significantly different between the two groups; 15% in the persistent cohort versus 7.5% in the non-persistent cohort (p = 0.311). Persistent SAB was associated with a variety of risk factors and significantly increased length of hospital stay. There was also a trend toward higher mortality rate in patients with persistent bacteremia.