Multi-regional clinical trials (MRCT) have become common practice in recent years in order to reach the study recruitment goal faster as well as increase the generalizability of trials findings to a global population. This is especially evident for disease areas where a large sample size is required for answer the scientific questions of interests, such as in trials of cardiovascular disease and osteoporosis. Because of the diverse population enrolled in the trials, potential geographic differences in treatment effect exist due to patient selection, patient management and factors contributing to outcome assessment. In the design stage of the trials, it would be very important to exam all baseline prognostic factors by geographic regions to understand the potential impact on treatment effect and take proper measures. In this presentation, statistical simulations will be presented to demonstrate the potential impact of study population from different geographic regions on an overall treatment effect.