Antibiotic prophylaxis has been employed to reduce the risk of infection. Many reports have documented the role of prophylactic antibiotics on the subsequent development of infection in patients undergoing surgical as well as a variety of percutaneous interventions including cardiac, vascular, biliary, genitourinary, and drainage of fluid collections. While prophylactic antibiotics can be critically important for certain procedures, their use can be associated with allergic reactions (including anaphylaxis), development of bacterial resistance, and increased costs of medical care. In this analysis, we report the incidence of clinical infection following minimally invasive interventions for dialysis access procedures. Hemodialysis (HD) and peritoneal dialysis (PD) patients undergoing consecutive percutaneous interventions (n = 3162) for HD and PD access were included in this study. Procedure-related clinical infection was defined as the presence of fever/chills, tenderness, erythema, swelling within 72 hours postprocedure. The procedures included percutaneous balloon angioplasty (arterial and venous) [n = 2078 (AVF = 1310; AVG = 768)], venography for vascular mapping (n = 110), endovascular stent insertion (n = 26), intravascular coil placement (n = 31), thrombectomy for an arteriovenous fistula (n = 106), thrombectomy for an arteriovenous graft (n = 110), tunneled hemodialysis catheter (TDC) insertion and exchange (n = 283), TDC removal (n = 160), and insertion of accidentally extruded TDC through the same exit site (n = 9). There were 260 peritoneal dialysis catheter insertions and 15 repositioning procedures. Only patients undergoing TDC insertion for accidentally extruded catheter and PD catheter placement received antibiotic prophylaxis within 1-2 hours before the procedure. Extruded TDC received 1 g of cefazolin while PD catheter insertion had 1 g of intravenous vancomycin. Povidone iodine was used for skin antisepsis in all cases. One patient (0.04%) postangioplasty and one patient (0.3%) after tunneled catheter placement developed clinical infection manifested by fever, chills, and malaise within 24 hours of the procedure. Both required hospitalization. Patient with angioplasty was a diabetic with an arteriovenous graft while TDC insertion was performed in a patient with advanced HIV. Percutaneous dialysis access procedure infections are generally low and might not warrant routine administration of antibiotic prophylaxis for all cases except for PD catheters and accidentally extruded TDC.