The use of bio-plasticizers, derived from natural oil and modified to improve the compatibility with PVC, represents a valid alternative towards the use of phthalate plasticizers, aimed to reduce the environmental and toxicological impact. Nevertheless, the substitution of phthalates is still very difficult to attain, due to high cost of bio-plasticizers. In addition, bio-plasticizes, contribute to the subtraction of resources to food chain, as is the case, for example, of epoxidated soybean oil. On the other hand, the potential of cardanol derivatives as PVC plasticizers was recently demonstrated. Compared to other bio-plasticizer, the cardanol derived plasticizers do not require the use of primary resources, and therefore do not contribute to the subtraction of resources to food chain. Therefore, this work is aimed to the development and property optimization of cardanol derived plasticizers. To this purpose, different plasticizers were produced though different epoxidation routes, characterized by low toxicological and environmental impact. The plasticizers are characterized by different yield of epoxidation of the alkyl chain double bonds. The properties of the cardanol derived plasticizers were compared to the properties of commercial plasticizers, either phthalates or natural derived. Mechanical properties were shown to be in the same range of other commercial plasticizers. The efficiency of the plasticizers was significantly improved by increasing the yield of epoxidation. Also, mechanical properties performed after ageing showed the excellent stability of the properties of the cardanol derived plasticizer characterized by the higher yield. Evaluation of the property retention index after ageing indicated that such plasticizers showed an improved stability of properties compared to other commercial plasticizer. The results obtained highlight the relevance of an high conversion of the double bonds into epoxies in order to produce high quality plasticizers.