OBJECTIVES: MRSA skin infections are associated with high morbidity and cost.  Little is known about real-world daptomycin effectiveness in relevant subpopulations.  We evaluated outcomes including time to response, duration of antibiotic therapy, and antibiotic-related hospital length of stay (AR-LOS) in subpopulations of patients with MRSA skin infections treated with daptomycin.  METHODS: Patients with MRSA skin infections were identified in a retrospective, multicenter, observational registry describing safety and real-world effectiveness of patients treated with daptomycin (Cubicin Outcomes Registry and Experience; CORE®). Investigators assessed patient outcome at the end of daptomycin therapy. Subpopulations of interest included those with reduced vancomycin susceptibility (MIC ≥2mcg/mL), the elderly, diabetics, and those with renal dysfunction.  RESULTS: A total of 137 patients were identified: 53% male, 33% >65yo, 31% diabetic, 6% CrCL <30ml/min. Of patients with vancomycin MICs, 14% were >2. Median daptomycin dose was 6mg/kg; 82% had prior antibiotics (66% of which was vancomycin).  Success occurred in 94% overall, and was 100% in first-line daptomycin, 93% as second line.  Time to clinical response ranged from 2-4 days with a median of 3 days for both first and second-line therapy.  Median AR-LOS tended to be greater among subpopulations: those with vancomycin MIC ≥2 [5 vs. 4 days], >65 yo [6 vs. 5 days], diabetics [6 vs. 4 days], and those with CrCL <30 [8 vs. 5 days], compared to those without each respective condition.  Total treatment duration (inpatient and outpatient days) ranged from 7-13 days, depending on clinical subgroup.  11/137 patients (8.3%) had AEs possibly related to daptomycin; discontinuation due to AE was 5.8%.  CONCLUSIONS: This evaluation of relevant patient populations provides meaningful information about real-world effectiveness of daptomycin-treated MRSA skin infections.  AR-LOS was longer in evaluated subgroups, particularly those with CrCL <30ml/min. Additional real-world evaluations, including comparative effectiveness studies are warranted to further evaluate relevant outcomes in various subpopulations with MRSA skin infections.