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Blending of thermoplastic polyurethane (TPU) with poly dimethyl siloxane rubber (PDMS) is an attractive approach, where one can combine the strength, toughness and biocompatibility of TPU with flexibility, inertness, high temperature resistance, low temperature flexibility and biocompatibility of PDMS. But the control of the factors determining the overall properties of such a blend like mixing time, temperature and rotor speed is difficult. Hence, an attempt has been made to optimize these processing parameters using statistical technique as per Taguchi. Four factors and three levels were chosen for carrying out the analysis using L9 Orthogonal Array as per Taguchi methodology. Tensile strength and impact strength of the blends under different processing conditions were evaluated as the quality characteristics. Analysis of Variance (ANOVA) was used in determining the significance of factors. The levels of significant factors were optimized using Signal to Noise ratio. It was found that a balance between the two properties were obtained when melt blending was carried out at 190 ̊C at 100 rpm rotor speed for 9 minutes for a blend of TPU with PDMS in the proportion of 70/30 by volume. Confirmatory tests were carried out to verify the optimized formulation. Blend morphology studies revealed that PDMS phase gets uniformly dispersed in a matrix of TPU. These blends are expected to be utilized for biomedical applications such as surgical implants and biomedical devices.