To improve the blood compatibility, the surface of polydimethylsiloxane (PDMS) films were irradiated using a CO2-pulsed laser. Acrylamide (AAm) was grafted onto a pre-irradiated surface. The AAm-grafted and laser-treated films were characterized using different techniques. Platelet adhesion and activation onto the AAm-grafted PDMS, laser-treated (ungrafted) and unmodified PDMS film surfaces were compared. Data from in vitro assays indicated that the platelet adhesion was reduced on the AAm-grafted PDMS and laser treated PDMS films in comparison with the unmodified PDMS. The laser-irradiated sample showed the minimum platelet adhesion. It seems that laser irradiation onto a silicone rubber surface is a versatile technique to produce anti-thrombogenic surface for biomaterial applications.