Purpose: Respiratory signal, binning method, and reconstruction algorithm are three major controllable factors affecting image quality in thoracic 4D cone-beam CT (4D-CBCT), which is widely used in image guided radiotherapy (IGRT). Previous studies have investigated each of these factors individually, but no integrated sensitivity analysis has been performed. In addition, projection angular spacing is also a key factor in reconstruction, but how it affects image quality is not obvious. An investigation of the impacts of these four factors on image quality can help determine the most effective strategy in improving 4D-CBCT for IGRT.