The purpose of this study was to evaluate whether low-profile totally implanted central venous port systems can reduce the late complication of skin perforation. Forty patients (age, 57 +/- 13 years; 22 females, 18 males) were randomized for the implantation of a low-profile port system, and another 40 patients (age, 61 +/- 14 years; 24 females, 16 males) received a regular port system as control group. Indications for port catheter implantation were malignant disease requiring chemotherapy. All port implantations were performed in the angiography suite using sonographically guided central venous puncture and fluoroscopic guidance of the catheter placement. Procedure time, number of complications (procedure-related immediate, early, and late complications), and number of explantations were assessed. Follow-up was performed for 6 months. All port implantations were successfully completed in both study groups. There were two incidents of skin perforation observed in the control group. One skin perforation occurred 13 weeks and the other 16 weeks after port implantation (incidence, 5%) in patients with regular-profile port systems. Two infections were observed, one port infection in each study group. Both infections were characterized as catheter-related infections (infection rate: 0.15 catheter-related infections per 1000 catheter days). In conclusion, low-profile port systems can be placed as safely as traditional chest ports and reduce the risk of developing skin perforations, which occurs when the port system is too tight within the port pocket.