With a focus on design methodology for developing a compact and lightweight minimally invasive surgery (MIS) robot manipulator, the goal of this study is progress toward a next-generation surgical robot system that will help surgeons deliver healthcare more effectively. Based on an extensive database of in-vivo surgical measurements, the workspace requirements were clearly defined. The pivot point constraint in MIS makes the spherical manipulator a natural candidate. An experimental evaluation process helped to more clearly understand the application and limitations of the spherical mechanism as an MIS robot manipulator. The best configuration consists of two serial manipulators in order to avoid collision problems. A complete kinematic analysis and optimization incorporating the requirements for MIS was performed to find the optimal link lengths of the manipulator. The results show that for the serial spherical 2-link manipulator used to guide the surgical tool, the optimal link lengths (angles) are (60°, 50°). A prototype 6-DOF surgical robot has been developed and will be the subject of further study.