This trial assessed the efficacy of cotrimoxazole lock solution in reducing catheter-related blood stream infections (CRBSIs) among hemodialysis (HD) patients who were dialyzed using tunneled catheters. Patients randomly received either heparin (2500 U/ml) (control group) or a mixture of 10 mg/ml cotrimoxazole (based on trimethoprim) and 2500 U/ml heparin (antibiotic group) as catheters lock solution. Compared with the control group, CRBSIs rates per 1000 catheter-days was significantly lower (0.58 vs 4.4 events; p = 0.002) and cumulative infection-free catheter survival was significantly higher (log rank statistic 5.88; p = 0.015) in the antibiotic group. There were no statistical differences regarding incidences of catheter removal (8.7% in the antibiotic group vs 22% in the control group; p = 0.116) or thrombosis (2.2% in the antibiotic group vs 9.8% in the control group; p = 0.129) between the two groups. cotrimoxazole containing catheter lock solution is effective in reducing CRBSIs incidence and prolonging dialysis catheter survival in HD patients.