The performance of a heat pipe is governed by many parameters, the effects of which may influence each other. Hence, it is utmost important to optimize the combination of these parameters for an effective energy transfer in a heat pipe. In the present study, the interacting effects of four different parameters affecting the effectiveness of heat pipe are studied namely the fluid filling ratio (20%, 30%, 40%), the pressure inside the heat pipe (0.2 bar, 1 bar, 1.8 bar), the number of wick layers (0, 1, 2) and the inclination angle of heat pipe (0°, 45°, 90°). The response surface method based on central composite design approach is applied to optimize the number of experiments. The effects of interacting parameters on the effectiveness of heat pipe are discussed. Among the various parameters, the pressure inside the heat pipe was found to be the most important parameter followed by the fluid filling ratio, the inclination of heat pipe and the number of wick layers. From the analysis, the optimum combination of parameters was obtained as 40% filling ratio, 0.2 bar pressure, 2 wick layers and 0° inclination. At this point, the effectiveness predicted with the model and obtained through experiments was found to be 0.630 and 0.649 respectively. Based on the experimental results, a quadratic empirical model is developed which predicts the effectiveness of heat pipe within [Formula: see text]% of the experimental results for different operating conditions of heat pipe.