Transmission mechanism is usually modeled as a rigid component in most control tasks of manufacturing processes. Nevertheless, experimental studies have shown that the inherent compliant characteristic of transmission mechanisms seriously degrades the whole system¡¦s performance. This paper presents an adaptive control strategy to overcome positioning difficulty of a transmission system with a variable compliance. A flexible joint, consisting of sixteen linear springs, is designed for actual positioning experiments. In order to enhance variation of the compliance, an eccentric load is located behind the flexible joint. Therefore, the axial compliance is not fixed and will change according to the load¡¦s angular position. The proposed controller is developed on an adaptive control structure to provide capability of fast adaptation to compliance variation. Besides, the robustness of the control system is also specifically emphasized to improve positioning performance with respect to model uncertainty and unknown disturbances. The control law is obtained by applying the Lyapunov¡¦s theorem. Effectiveness of the presented control method is demonstrated on trajectory control of an experimental transmission mechanism with the flexible joint under variable compliance conditions.