This paper reports the results of an in vitro investigation into the blood response of medical grade poly (vinyl chloride) (PVC), and two types of plasticized PVC in tubing or sheet form, with di-(2-ethylhexyl)phthalate (DEHP) and di(isononyl) cyclohexane-1,2-dicarboxylate (HEXAMOLL(®) DINCH) as plasticizer, were selected for assessment of complement activation, coagulation system and platelet activation. The results of the study show that not only the plasticizers at PVC surface have an influence on complement activation, but also the incubation condition such as incubation time and the diameter of PVC tubing. Under static status, C3a, C5a and SC5b-9 concentration in the blood were higher after contacting with PVC plasticized with DEHP (PVC1) than after contacting with PVC plasticized with DINCH (PVC2). However, under dynamic circulation, the results were totally converse, which may be due to smaller diameter and higher shear rate of PVC2. In addition, there was a significant increase of activated partial thrombin time (APTT) and decrease of FIX concentration after plasma contacting with the PVC tubing, which indicated that the intrinsic pathway may be impacted when blood contacted with PVC tubing. However, there was no significant difference of APTT, FIX concentration and CD62p expression rate between the two materials. Moreover, the migration in the DINCH system was considerably lower than for DEHP, which indicates that DINCH could be a promising alterative plasticizer of DEHP.