Fungal periprosthetic joint infections (PJI) are difficult to treat, due to important biofilm formation and limited local penetration of systemically administered antifungals. Calcium sulphate (CaSO ₄ ) might be a promising carrier to increase local concentration of antifungals. We hypothesized that local amphotericin B release from CaSO ₄ is high enough to significantly contribute to treatment of fungal PJI. We report joint fluid and serum concentrations of amphotericin B after local application with CaSO ₄ as an implanted resorbable carrier material as adjunct to standard surgical and systemic antifungal treatment in two cases of PJI with Candida spp. Maximal joint fluid amphotericin B concentration was 14.01 mg/L 5 days after the second local administration of liposomal amphotericin in Case One and 25.77 mg/L 14 days after the second local administration in Case Two. Concentrations higher than minimal inhibitory concentrations (MIC) could be measured for 21 days and 17 days after local administration in Case One and Two, respectively. In Case Two, serum concentration of amphotericin B was <0.01 mg/L 3 days after local administration of 450 mg liposomal amphotericin B. No local or systemic adverse reaction was observed. Fungal PJI was successfully eradicated in both cases with a follow-up of 12 months in Case One and 20 months in Case Two. Application of amphotericin B-loaded CaSO ₄ was associated with joint fluid concentrations higher than minimal inhibitory concentrations for Candida spp. for approximately 3 weeks, with the advantage that the carrier material dissolves spontaneously and does not require secondary removal. Relapse of fungal infections did not occur in these two patients.