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Background: Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CoNS) is increasingly common and is sometimes treated with off-label use of linezolid. Methods: We conducted a retrospective study of patients with PJI caused by CoNS treated with surgical intervention and orally administrated linezolid during the period 1995-2014 ( n  = 28). Clinical outcomes and adverse events related to linezolid administration were evaluated. Mean time to follow-up was 4.3 years (range: 0.2-12). Results: Twenty-two of 28 patients were infection-free at follow-up. No CoNS strain was resistant to vancomycin, but 16 of 28 were resistant to rifampicin, 23 of 28 to clindamycin and 20 of 27 to quinolones. The mean duration of linezolid treatment was 4.2 weeks (range: 1-12). Eleven of 28 patients had an adverse event related to the antimicrobial treatment, and four had to discontinue linezolid, but all adverse events were reversible within 2 months after discontinuation. Conclusions: Oral linezolid administration combined with adequate surgical treatment may be useful for the treatment of PJIs caused by CoNS.