ABSTRACT Introduction: Fungal peritonitis is a uncommon but important complication of continuous ambulatory peritoneal dialysis (CAPD). It accounts for 5%-15% of the total burden of peritonitis in most CAPD units. At the National Kidney & Transplant Institute (NKTI), the incidence increased from 11% in 1997 to 21% in 2000. Since this complication is associated with severe morbidity, CAPD dropout and death, measures to decrease or prevent its occurrence are necessary. Objectives: To determine if Nystatin is effective as prophylaxis for fungal peritonitis in patients with an on-going CAPD-related bacterial peritonitis and to determine its predisposing factors. Design: Prospective randomized open blinded endpoint trial (PROBE) Setting: Tertiary renal referral center Methods: From June 2001 to December 2004, newly diagnosed patients with end stage renal disease (ESRD) on CAPD were randomized to receive Nystatin as prophylaxis for fungal peritonitis during their first bacterial peritonitis episode and for all successive episodes within the next 6 months. Group 1 patients received Nystatin concomitantly with the antibiotics for bacterial peritonitis while Group 2 received the antibiotics alone. The incidence and the time to development of fungal peritonitis were measured. Demographic data, primary renal disease, CAPD system used, and the number of episodes of bacterial peritonitis after inclusion into the study were collected. Intention to treat analysis was used. Results: One hundred thirty-three patients fulfilled the criteria for inclusion in the study; 74 patients were randomized to Group 1and 59 patients were randomized to Group 2. The patients were followed up to 6 months. A total of 83 patients completed the study: 47 in Group 1 and 36 in Group 2. Group 1 had a slightly lower incidence of fungal peritonitis compared to Group 2 (10.6% vs 11.1%) but this was not statistically significant (p=1.0). The cumulative incidence of developing fungal peritonitis was 10.8%. Nystatin prophylaxis delayed the time to develop fungal peritonitis by 5 months but this was not statistically significant (p=0.9417). Only the presence of diabetes mellitus predisposed to the development of fungal peritonitis. Conclusion: There was a tendency to delay the development of fungal peritonitis with the use of Nystatin prophylaxis within the first 5 months of a bacterial peritonitis episode. It may be useful to delay the early incidence of fungal peritonitis among CAPD patients with known risk factors for this complication.