PURPOSE: For critically ill patients undergoing continuous renal replacement therapy (CRRT), daptomycin dosing recommendations are scarce. We, therefore, retrospectively assessed routinely measured daptomycin plasma concentrations, daptomycin dose administered and microbiological data in 11 critically ill patients with Gram-positive infections that had received daptomycin once daily. METHODS: The retrospective analysis included critically ill patients treated at the intensive care unit (ICU) who had daptomycin plasma concentrations measured. RESULTS: Daptomycin dose ranged from 3 to 8 mg/kg/q24 h in patients undergoing CRRT (n = 7) and 6 to 10 mg/kg/q24 h in patients without CRRT (n = 4). Peak and trough concentrations showed a high intra- and inter-patient variability in both groups, independent of the dosage per kg body weight. No drug accumulation was detected in CRRT patients with once-daily daptomycin dosing. Causative pathogens were Enterococcus faecium (n = 6), coagulase-negative Staphylococcus (n = 2), Staphylococcus aureus (n = 2) and unknown in one patient. Microbiological eradication was successful in 8 of 11 patients. Two of three patients with unsuccessful microbiological eradication and fatal outcome had an Enterococcus faecium infection. CONCLUSION: In critically ill patients undergoing CRRT, daptomycin exposure with once-daily dosing was similar to ICU patients with normal renal function, but lower compared to healthy volunteers. Our data suggest that daptomycin once-daily dosing is appropriate in patients undergoing CRRT.