This paper presents an efficient tool path plan for machining the impeller with a 5-axis numerically controlled machine. A method of assigning key tool orientations is reported and B-spline interpolation is used to produce smooth and interference-free tool orientation. The final tool paths generated by the proposed method are verified by using the cutting simulation function. A machining experiment is performed on a Mikron machine tool. Experimental results show that the present method is feasible and can produce interference-free tool path.