Knowledge of frictional forces acting on the tips of minimally invasive medical devices is important in the design and simulation of such devices. Moreover, several studies have shown that uncontrolled frictional forces can induce damage to organs. The goal of this study is to empirically investigate the dominant factors affecting frictional forces between a bovine cardiac tissue and a catheters tip. A dedicated apparatus is developed to reproduce the sliding contact between a cylindrical element and the cardiac tissue. In this paper, we utilize the design of experiment (DOE) approach to study friction. Factorial designs (FD) are used to reduce the number of experiments without reducing the information that could be extracted. Twelve factors were selected to represent the main parameters that could potentially affect friction. These factors are of physical, geometrical, physiological and temporal nature. As a result of 4 factorial designs representing a set of 128 experiments, we studied the impact on friction of the 12 parameters as well as the interactions between them. As expected, the normal force applied on the cylindrical tip is the dominant factor affecting the friction force. The remaining significant effects are the cylinder pitch angle, tissue physiological state and the pressure applied on the cardiac tissue expressed in cylinder dimensions. This study gives some guidelines to minimize and control friction interactions between a cylindrical tip and a tissue.