Tunneled, cuffed central vein catheters (TCC) are widely used for delivering hemodialysis (HD). Among the complications associated with central vein catheters in HD patients, infection is the principal cause of morbidity and mortality. The optimal strategy for management of TCC infections is unclear. This prospective study was aimed at assessing the efficacy of antibiotic-lock therapy using vancomycin and gentamycin in preventing catheter-related blood stream bacterial infection in patients on HD. A total of 63 HD patients with 81 TCC were enrolled at the time of catheter insertion. Patients were randomized into two groups: Group I (33 patients, 37 insertions) included TCC with antibiotic lock therapy and Group II (30 patients, 44 insertions) with routine TCC management. Infection-free catheter survival of both groups was evaluated and compared at the end of the 12-month study period. A total of 57 TCC infections were encountered with an incidence rate of 8.95 infections per 1000 dialysis sessions (DS). The rate of infection was significantly lower in Group I (4.54 per 1000 DS) as compared to Group II (13.11 per 1000 DS), p 0.05). Our study suggests that antibiotic-lock therapy using a combination of vancomycin and gentamycin is useful in preventing catheter-related blood stream infection in patients on HD.