Peritoneal dialysis (PD) related infections are a significant obstacle leading to PD discontinuation. Since catheter related infections (CRI), defined as exit site infections and/or tunnel infection, can progress to peritonitis, vigorous efforts are implemented in CRI prevention. Following an increased CRI rate in our institution, partially related to environmental organisms found in water distribution systems, we hypothesized that exit site care that includes prevention of water exposure-related pathogens may reduce CRI. In this prospective single center study, we compared a contemporary cohort consisting of PD patients who implemented the modified exit-site care protocol, mainly including water avoidance during shower with stoma bag usage and local Mupirocin ointment against a historical control group before the protocol implementation. The historical cohort was allowed water exposure and used local gentamicin ointment. The primary outcome was the development of a CRI. Secondary outcomes were PD associated peritonitis and infection related outcomes. There were 55 patients in contemporary cohort and 58 in historical group. The CRI rate was significantly lower in study group (0.11/episodes per patient year [EPP]) compared to control group (0.71 EPP), p < 0.001. A multivariate Cox regression analysis demonstrated a protective effect of being in the contemporary cohort compared to historical group (HR for first CRI = 12.0 95%CI: 4.0-35.7, p < 0.001). Peritonitis rate was significantly lower in contemporary cohort (0.19/EPP) compared to the historical group (0.40/EPP), p = 0.011. Transfer to hemodialysis was significantly lower in contemporary cohort than historical group (7.3% vs 31.0% in contemporary and historical group respectively, HR = 0.2, 95%CI; 0.05-0.6, p = 0.001). An exit site care protocol that includes water avoidance and local Mupirocin use reduced substantially both CRI and peritonitis rate in patients treated with PD.