Image guidance has become the standard of care for patient positioning in radiotherapy, where image registration is often a critical step to help manage patient motion. However, in practice, verification of registration quality is often adversely affected by difficulty in manual inspection of 3-D images and time constraint, thus affecting the therapeutic outcome. Therefore, we proposed to employ both bootstrapping and the supervised learning methods of linear discriminant analysis and random forest to help robustly assess registration quality in ultrasound-guided radiotherapy. We validated both approaches using phantom and real clinical ultrasound images, and showed that both performed well for the task. While learning-based techniques offer better accuracy and shorter evaluation time, bootstrapping requires no prior training and has a higher sensitivity.