The prevalence of infections caused by methicillin-resistant organisms has increased, causing difficulty in the treatment of prosthetic joint infection. A multicenter study was performed to review 50 patients with deep infections with or without a resistant organism, such as methicillin-resistant Staphylococcus aureus, at the site of total knee arthroplasty. A group of 13 patients with early deep infections and 4 patients with acute hematogenous infections underwent treatment with debridement, antibiotic therapy, and retention of the prosthesis with revision of the polyethylene insert. Thirty-three patients with late chronic infections were treated with challenging prosthesis retention for prostheses that had not loosened or 2-stage exchange arthroplasty for prostheses that had loosened. Mean duration of follow-up was 4.7±1.8 years. No significant differences in resultant functional knees and mean number of operations were observed between 7 patients with resistant early deep infections and 6 patients with nonresistant early deep infections. However, 24 patients with nonresistant chronic infections showed significant improvement in resultant functional knees (24 of 24; 100%) and fewer mean operations (2.8 times) compared with 9 patients with resistant chronic infections (1 of 9, 11%, and 4.3 times, respectively). The remaining 8 patients with resistant chronic infections (89%) had arthrodesis (3 patients) or underwent above-the-knee amputation (1 patient) or spacer arthroplasty (4 patients). Although patients with resistant early postoperative deep infections showed good results that were similar to those in patients with nonresistant early infections, those with resistant late chronic infections had a significantly inferior success rate compared with those who had nonresistant late chronic infections.