Immuno-compromised patients are at high risk for all kind of infections. Unfortunately, they need central venous catheters (CVCs), which are associated with infectious complications. In this study we examined the effectiveness of chlorhexidine-silver sulfadiazine impregnated CVCs to prevent catheter-related infections in patients receiving high-dose chemotherapy followed by peripheral stem cell transplantation. This historical cohort study evaluated 139 patients of whom 70 patients were provided with non-impregnated CVCs and 69 patients with impregnated CVCs. Patients were treated for different diagnoses. The median number of days a CVC stayed in situ was 18 in the non-impregnated group and 16 in the impregnated group. The median duration of neutropenia of patients with non-impregnated CVCs was 9 days compared with 7 days of patients with impregnated CVCs. We found less catheter colonization (CC) in patients with chlorhexidine-silver sulfadiazine CVCs (RR 0.63, 95% CI 0.41-0.96; P = 0.03). Catheter-related blood stream infections (CR-BSI) were also diminished, but this result was not statistically significant (RR 0.15, 95% CI 0.02-1.15; P = 0.06). The reduction in CC and CR-BSI did not diminish the incidence of fever. We conclude that the use of chlorhexidine-silver sulfadiazine impregnated CVCs provide an important improvement in the attempt to reduce CC and CR-BSI.