Gaining information about heart and coronary arteries such as estimating the flow velocity and coronary flow reserve (CFR) by only using 2D + time X-ray angiography sequence is of great interest due to its availability. We propose to segment the coronary arteries from 2D+time X-ray angiography sequences during contrast fluid propagation, by using a multi-step method based on unsharp masking followed by an iterative process of segmenting and non-rigid registration, until the alignment from the registration process is satisfactory. The proposed method is evaluated using 11 sets of angiography sequences, and the results showed 97% accuracy, 99% specificity, and 93% sensitivity in segmentation of the coronary arteries compared to more than 4000 manually marked points.