In-situ sample holders with double-tilting capabilities are used to insert and position samples inside a transmission electron microscope for dynamic imaging. However, the performance of these sample holders, regarding energy-dispersive X-ray spectroscopy (EDS) analysis, is not on par with their single-tilt counterparts. By analyzing the EDS influences and the tilting mechanism of double-tilt sample holders, the need for a remote-center-of-motion (RCM) mechanism as a tilting mechanism is identified. Because existing RCM mechanism design strategies limit the design flexibility, a novel design strategy is developed. The novel strategy gives more flexibility in terms of the use of space, design for stiffness and it gives variable input/output link rotation ratio functionality. A compliant proof-of-principle mechanism, which is designed using the novel RCM mechanism design strategy, is manufactured to characterize the accuracy, force/displacement behavior and the input/output link rotation ratio. Analytical, numerical and experimental results are compared, and it can be concluded that the compliant RCM mechanism has potential to be used in double-tilt sample holders.