Systems and methods for vision-based position and orientation determination for endovascular tools are disclosed. In one example, a method includes receiving a two-dimensional medical image including a view of at least a distal portion of a medical instrument, the distal portion of the medical instrument including one or more fiducials positioned thereon, the one or more fiducials being radio-opaque and visible in the medical image. The method also includes detecting, within the medical image, a two-dimensional appearance of the one or more fiducials, and based on the two-dimensional appearance of the one or more fiducials, determining at least one of a roll angle of the distal portion of the medical instrument, and an incline of the distal portion of the medical instrument.