A good vascular access is the lifeline of patients on long-term hemodialysis (HD) and anteriovenous fistula is considered the ideal access. Vascular access related septicemia (VARS) is the second most common cause of mortality among HD patients. Such infections could also lead to loss of vascular access unless specific measures are taken to preserve the accesses. The present study was designed to determine the incidence of septicemia, common bacterial flora involved, and impact of early, empirical antibiotic therapy on vascular access salvage among HD patients. This prospective study, involved 209 patients, undergoing long-term HD, from June 1996 to June 2000. A total of 85 (40.6%) developed VARS with predominance in females (63.7%), patients above 50 years of age (37.0%) and those having diabetes mellitus (25.1%). A total of 124 episodes of septicemia were recorded with an average of 1.23 episodes per 100 patient-months during the four year (10032 patient-months) study period. Peripheral blood samples for culture and sensitivity were collected and the patients were started empirically on amikacin-vancomycin combination which was modified after obtaining culture and sensitivity results. A cure was defined as 45 days symptom-free interval after antibiotic therapy was completed. Staphylococcus aureus was the commonest (29.0%) organism associated with VARS, followed by Pseudomonas aeruginosa (15.3%). The temporary vascular access group recorded maximum number of VARS episodes; [femoral catheter (FC) group, (43.5%), followed by subclavian (SC) group, (28.2%)] and the lowest (8.8%) was seen in the AVF group. Vascular access salvage rate of 48/85 (56.4%) and mortality of 22/85 (25.9%) was observed in the present study. Antibiotic access salvage with Amikacin-Vancomycin combination has an advantage of preserving vascular access sites in at least, 50% of cases.