Oscillating heat pipes (OHPs) are very promising cooling devices. Their heat transfer performance is affected by many factors, and the form of the relationship between the performance and the factors is complex and non-linear. In this paper, the effects of charging ratio, inclination angle, and heat input and their interaction effects on heat transfer performance of a looped copper-water OHP are analyzed. First, suppose that the relationship between the response and the variables approximates a second-order model. And use the central composite design to arrange the experiment. Then, the method of least squares is used to estimate the parameters in the second-order model. Finally, multivariate variance analysis is used to analyze the model. The results show that the assumption is right, that is to say, the relationship is well modeled by a second-order function. Among the three main effect variables, the effect of inclination angle is the most significant, but their interaction effects are not significant. In the range of the considered factors, both the optimum charging ratio and the optimum inclination angle increase as the heating water flow rate increases.