Efficacy and safety of antibiotic 'locks', in prevention of thrombotic and infectious complication-related morbidity and mortality, among diabetics dialyzed through tunneled-cuffed catheters (TCCs) has not been effectively investigated. This trial was designed to investigate the outcome of TCCs (n = 109), inserted among 96 diabetic end-stage renal disease patients (March 2002-February 2003), by comparing the catheter thrombosis, catheter-related bloodstream infections (CRBSI), catheter survival, and mortality rates, between the cohorts of 49 patients who had TCCs (n = 51) 'locked' with cefotaxime/heparin (group I) and 47 patients with TCCs (n = 58) filled with standard heparin (group II). Thrombosis was defined as the inability to use catheter at a blood flow of 200 ml/min despite intraluminal thrombolysis. Primary end points were catheter thrombosis and CRBSI; elective catheter removal and CRBSI-related death led to sensor of TCCs follow-up. Patients with intraluminal cefotaxime/heparin lock, on cumulative survival analysis, showed a superior thrombosis-free (86.3 vs 63.8%, P = 0.023, log rank), infection-free (72.9 vs 27.1%, P = 0.004, log rank), and thrombosis- and infection-free TCC survival (78.4 vs 37.9%, P = 0.001, log rank) at 365 days, besides having significantly lower incidence of CRBSI (1.56 vs 3.68 episodes/1000 catheter days, P < 0.0001) and CRBSI-related mortality (9.8 vs 23.4%, P = 0.015), compared with the heparin-alone group. Deployment of cefotaxime-heparin 'lock' enhances catheter survival; reduces thrombotic and infectious complications and ensuing mortality, among diabetics on dialysis. However, further studies are needed to define the long-term implications of antibiotic locks in terms of the risk of emergence of antimicrobial resistance.