A majority of osteoarticular and implant-related infections are due to staphylococci and biofilm formation. Combined therapy including rifampicin is frequently recommended. Indeed, rifampicin penetrates biofilms and kills adherent staphylococci, but cannot be administered as monotherapy because of the rapid emergence of resistant mutants. While several antibiotic combinations including rifampicin have been implemented, evaluation of the clindamycin-rifampicin combination has been neglected, presumably because of the emergence of alternative combinations, such as quinolone-rifampicin, and the fear of potential antagonistic interactions. We report a limited series of 20 patients (3 immune-suppressed) with 6 arthroplasty infections, 4 other implant infections, 7 native arthritis, and 3 osteomyelitis, who were all successfully treated with this oral combination for >75% of the antibiotic course (median duration 45 days). The excellent outcomes obtained with this antimicrobial combination after a mean follow-up of 2.6 y (range 1.0-6.1 y) warrant further clinical and microbiological studies for implementing this regimen in routine practice.