Peritoneal dialysis-associated peritonitis from such resistant organisms as vancomycin-resistant enterococci increasingly is occurring and is challenging to treat. We describe 2 cases of vancomycin-resistant entercoccus peritonitis successfully treated with intraperitoneal daptomycin. Both patients were on automated peritoneal dialysis therapy with culture-positive vancomycin-resistant Enterococcus faecium peritonitis and were treated with 10 to 14 days of intraperitoneal daptomycin given every 4 hours through manual peritoneal dialysate exchanges. Despite the known degradation in dextrose solutions, intraperitoneal daptomycin was effective in clearing both infections. Neither patient experienced a relapse or repeated peritonitis. Additional studies of dosing and pharmacokinetics of intraperitoneal daptomycin in the treatment of patients with vancomycin-resistant enterococcus peritonitis are needed.