SummaryBackground and objectives The effect of biocompatible peritoneal dialysis (PD) solutions on PD-related peritonitis is unclear. This study sought to evaluate the relationship between use of biocompatible solutions and the probability of occurrence or clinical outcomes of peritonitis.Design, setting, participants, & measurements The study included all incident Australian patients receiving PD between January 1, 2007, and December 31, 2010, using Australia and New Zealand Dialysis and Transplant Registry data. All multicompartment PD solutions of neutral pH were categorized as biocompatible solutions. The independent predictors of peritonitis and the use of biocompatible solutions were determined by multivariable, multilevel mixed-effects Poisson and logistic regression analysis, respectively. Sensitivity analyses, including propensity score matching, were performed.Results Use of biocompatible solutions gradually declined (from 7.5% in 2007 to 4.2% in 2010), with preferential use among smaller units and among younger patients without diabetes mellitus. Treatment with biocompatible solution was associated with significantly greater overall rate of peritonitis (0.67 versus 0.47 episode per patientyear; incidence rate ratio, 1.49; 95% confidence interval [CI], 1.19 to 1.89) and with shorter time to first peritonitis (hazard ratio [HR], 1.48; 95% CI, 1.17 to 1.87), a finding replicated in propensity score-matched cohorts (HR, 1.36; 95% CI, 1.09 to 1.71).Conclusions In an observational registry study, use of biocompatible PD solutions was associated with higher overall peritonitis rates and shorter time to first peritonitis. Further randomized studies adequately powered for a primary peritonitis outcome are warranted.