Infection, thrombosis, and stenosis are among the most common complications of blood-contacting catheters and are caused by surface properties of the substrate materials. Ion beam-based processes such as ion implantation and ion beam-assisted deposition affect only the outer micron of the treated material surface; there is little effect on bulk properties. These processes were therefore used on common catheter materials, and their biological properties were evaluated. Ion implantation of materials such as silicone rubber resulted in a less tacky, more wettable surface that demonstrated thrombus-resistance in both in vivo and preliminary clinical studies. Ion beam-assisted deposition was used to deposit silver-based coatings, which demonstrated antimicrobial activity in in vitro and clinical studies. Biocompatibility of these processed catheter materials was also demonstrated using simple laboratory studies. These processes, therefore, can be readily applied to blood-contacting catheters to make them thrombus- and infection-resistant.