BACKGROUND: Septic arthritis (SA) is a dangerous condition that requires emergency treatment. Managed by culture-specific antibiotics, irrigation, and debridement (I&D), some patients require repeat surgical treatment. The objectives were to determine the risk factors for SA and risk factors for repeat arthroscopic I&D in SA patients. We hypothesized that variables which directly or indirectly contributed to a larger infection burden would be associated with the development of SA and the need for repeat arthroscopic I&D. METHODS: All patients ≥ 18 years old presenting to the emergency department, orthopaedic and rheumatology clinics at our major trauma centre between January 2018 and January 2020 with a hot, swollen joint were retrospectively evaluated. Patients with previous trauma and metalwork in the affected joint, periprosthetic joint infection, previous joint arthroplasty surgery, soft tissue infection, missing data, transferred to another centre, diagnosis not concerning the joint, and < 24-month follow-up were excluded. Two hundred eleven patients were included (SA: 28; pseudogout: 32; gout: 50; others: 101). Variables of interest in the 3-month period preceding the diagnosis of SA were compared between SA and non-SA patients using univariable analysis. A multivariable logistic regression model was formed using covariates with corresponding univariable tests of p < 0.200. Similar analyses were performed to compare SA patients with multiple washouts/procedures with those with one washout/procedure. RESULTS: Multivariable analysis showed multiple risk factors for SA, namely rheumatoid arthritis (RA) (OR: 3.4; 95% CI: 1.2-10.0; p = 0.023); skin infection (OR: 3.3; 95% CI: 1.2-9.0; p = 0.017), liver disease (OR: 9.9; 95% CI: 2.2-43.9; p = 0.003), knee joint involvement (OR: 3.5; 95% CI: 1.3-9.4; p = 0.014), and use of immunosuppressive medication (OR: 3.5; 95% CI: 1.2-10.6; p = 0.027). Risk factors for multiple washouts included synovial WBC levels > 10.5 × 109 cells/L (OR: 3.0; 95% CI: 2.3-38.8; p = 0.009) and RA (OR: 3.5; 95% CI: 1.9-66.3; p = 0.017). CONCLUSIONS: These findings suggest that prophylactic actions against septic arthritis should be targeted at patients with liver disease, RA, or skin infection. Repeat arthroscopic I&D of septic joints may be needed, especially in patients with synovial WBC levels > 10.5 × 109 cells/L and RA. Key Points • The risk factors for septic arthritis determined in this study are rheumatoid arthritis, skin infection, liver disease, knee joint involvement, and immunosuppressant usage. • Some septic arthritis patients need multiple rounds of arthroscopic irrigation and debridement. The risk factors for this are a synovial WBC count > 10.5 × 109 cells/L and rheumatoid arthritis.