<b><i>Introduction:</i></b> Loss of residual renal function (RRF) as well as high peritoneal glucose exposure are associated with increased peritonitis frequency in peritoneal dialysis (PD) patients. Our objective was to investigate the contribution of RRF and peritoneal glucose exposure to peritonitis in PD patients. <b><i>Methods:</i></b> In this prospective longitudinal cohort study, 105 incident end-stage renal disease patients that started PD between January 2006 and 2015 were studied. Follow-up was 5 years with censoring at death or switch to another treatment modality. Cox regression models were used to calculate the association between glucose exposure, RRF, and peritonitis. Kaplan-Meier analysis was used to examine the difference in occurrence of peritonitis between patients with high and low glucose exposure and between those with and without residual diuresis. <b><i>Results:</i></b> One hundred and five patients were followed for a mean of 23 months. Fifty-one patients developed a peritonitis. Cox regression models at 6 months showed that glucose exposure and not residual diuresis significantly predicted PD peritonitis. Kaplan-Meier analysis after 6 months of follow-up showed that time to first PD peritonitis was significantly longer in the low glucose exposure group. Similarly, patients with RRF had a significantly longer interval to first peritonitis compared to patients without RRF. <b><i>Conclusion:</i></b> A higher exposure to glucose rather than loss of RRF is associated with an increased risk of peritonitis. This confirms the detrimental effects of glycemic harm to the peritoneal host defense on invading microorganisms and argues for the use of the lowest PD glucose concentrations possible.