BACKGROUND: Candida periprosthetic joint infection (CPJI) is a rare, difficult-to-treat disease. The purpose of this study was to evaluate the clinical characteristics and outcomes of CPJI treated with various surgical and antifungal strategies. METHODS: We conducted a multicenter retrospective study of all CPJI diagnosed between 2003 and 2015 in 16 Spanish hospitals. RESULTS: Forty-three patients included: median age, 75 years, and median Charlson Comorbidity Index score, 4. Thirty-four (79.1%) patients had ≥1 risk factor for Candida infection. Most common causative species were C. albicans and C. parapsilosis. Thirty-five patients were evaluable for outcome: overall, treatment succeeded in 17 (48.6%) and failed in 18 (51.4%). Success was 13/20 (67%) in patients with prosthesis removal and 4/15 (27%) with debridement and prosthesis retention (p = 0.041). All 3 patients who received an amphotericin B-impregnated cement spacer cured. In the prosthesis removal group, success was 5/6 (83%) with an antibiofilm regimen and 8/13 (62%) with azoles (p = 0.605). In the debridement and prosthesis retention group, success was 3/10 (30%) with azoles and 1/5 (20%) with antibiofilm agents. Therapeutic failure was due to relapse in 9 patients, need for suppressive treatment in 5, persistent infection in 2, and CPJI-related death in 2; overall attributable mortality was 6%. CONCLUSIONS: CPJI is usually a chronic disease in patients with comorbidities and risk factors for Candida infection. Treatment success is low, and prosthesis removal improves outcome. Although there is insufficient evidence that use of antifungals with antibiofilm activity has additional benefits, our experience indicates it may be recommendable.