Background A reliable central venous access device is a cornerstone in the treatment of cancer. Both peripherally inserted central catheters (PICC) and totally implanted chest ports (PORT) are commonly used for the delivery of chemotherapy. Both types of catheter can cause adverse events such as catheter-related deep venous thrombosis (CR-DVT), infection and mechanical complications. Method We conducted a randomized controlled trial including 399 patients with cancer and performed a health economic evaluation investigating the cost related to PICCs and PORTs using several clinically relevant dimensions from a healthcare perspective. The cost was determined using process and cost estimate models. Result PICCs are associated with a higher total cost when compared with PORTs. Combining the costs of all categories, the prize per inserted device was 824.58 EUR for PICC and 662.34 EUR for PORT. When adjusting for total catheter dwell time the price was 6.58 EUR/day for PICC and 3.01 EUR/day for PORT. The difference in CR-DVT was the main contributor to the difference in cost. The daily cost of PICC is approximately twice to that of PORT. Conclusion We have demonstrated that the cost from a healthcare perspective is higher in cancer patients receiving a PICC than to those with a PORT. The difference is driven mainly by the cost related to the management of adverse events. Our findings are relevant to anaesthetists, oncologists and vascular access clinicians and should be considered when choosing vascular access device prior to chemotherapy.