Anti-collision analysis has been becoming even more important in the past few years with the increasing amount of wells drilled in highly congested fields. The separation factor (SF) is a critical safety parameter to avoid wellbore collisions, where the pedal curve method (PCM) is the commonly used way for the SF calculation. However, such method may be conservative in many situations and possibly triggers an unnecessary early stop drilling due to its conservation. In this study, our work aims to evaluate and compare the different types of the SF models. In addition, an alternative and supplement method of the PCM, called as elliptic cylinder of uncertainty (ECoU) method, is proposed. The radius of the ECoU considers the distance of the intersecting points of the center-to-center line and the cylinder surfaces of both reference and offset wells. By introducing the cylinder surfaces into the SF calculation, it could extend the collision avoidance along the whole well path to reduce multiple-points collision possibility. The findings in the study help us for better understanding of the SF analysis and also show that using the ECoU indication has a great potential in fields applications as a viable method to keep the drilling operations’ safety.