Background. Multi-drug resistant bacteria are a growing concern in healthcare. Daptomycin is being used with increasing frequency in the treatment of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in hemodialysis (HD) patients. Thrice-weekly dosing of daptomycin in this population would allow for coordination of dosing with common outpatient HD schedules. The aim of this study is to determine if thrice-weekly dosing of daptomycin is equivalent to dosing every 48 hours in patients receiving chronic intermittent hemodialysis. Equivalence will be assessed with regard to microbiological cure, clinical cure, hospital length of stay, and mortality. Methods. All patients with positive blood cultures who received at least one dose of daptomycin between January 1st 2009 and December 31st 2010 at Indiana University Health Methodist and University Hospitals were identified. Adult patients with end-stage renal disease on a stable thrice-weekly hemodialysis regimen, confirmed VRE or MRSA bacteremia, and at least three doses of inpatient daptomycin therapy were enrolled in the study. Results. Twelve patients met criteria for inclusion in this study. Nine received daptomycin every 48 hours for the treatment of bacteremia, and three received daptomycin thrice-weekly after dialysis. There was no difference in time to clearance of blood cultures between the Q48H and thrice-weekly groups (2.11±2.15 days vs. 4.33±4.16 days; p=0.241).Length of hospital stay was not statistically significantly different between the two groups (22.8 days vs. 14.9 days; p=0.065).Conclusions. Thrice-weekly dosing of daptomycin may be effective for the treatment of bacteremia in hemodialysis patients.