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Objectives: Septic polyarthritis is rarer than septic monoarthritis, but associated with higher mortality. Septic polyarthritis may be difficult to distinguish clinically from noninfectious inflammatory arthritis. We describe one of the largest samples of septic polyarthritis with the aim of distinguishing septic monoarthritis from polyarthritis., Methods: We conducted a retrospective study of adults admitted to tertiary care with septic monoarthritis and polyarthritis. Baseline characteristics, microbial profiles, joint involvement, length of stay, and 60-day readmission rates were determined., Results: We identified 464 and 42 cases of septic monoarthritis and polyarthritis, respectively, including 7 cases of septic polyarthritis with comorbid rheumatoid arthritis. Compared to those with septic monoarthritis, patients with septic polyarthritis were more likely to have rheumatoid arthritis (P<0.01), sepsis (P<0.01), and higher peripheral (P<0.001) and synovial (P<0.001) white blood cell counts. Operative intervention rates were similar, but mean length of stay was longer in polyarticular septic arthritis (P<0.001). Patients with septic polyarthritis with/without underlying rheumatoid arthritis were similar in terms of presenting features and outcomes, except for more frequent immunosuppressive therapy in rheumatoid arthritis (P<0.01)., Conclusions: In this sample of patients with septic arthritis, patients with septic polyarthritis were more likely to have systemic infection at presentation than those with septic monoarthritis. Despite this difference, patients with septic monoarthritis and polyarthritis tended to have similar outcomes. While rheumatoid arthritis was observed more frequently among patients with septic polyarthritis, those with/without underlying rheumatoid arthritis had similar presenting features and outcomes., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)