Optimised pCASL protocols may still be sensitive to macrovascular contamination (MVC), leading to high CBF estimation error. In this study, we conducted a systematic investigation of CBF sensitivity to MVC from a comprehensive set of optimal pCASL protocols. The general kinetic model was only robust for CBF estimation when tissue ATT was less than 1.5s. An extended kinetic model could reduce CBF sensitivity to up to 2.3s. The results of CBF sensitivity maps could be used for examining a protocol for possible MVC effects before scanning, or data interpretation afterwards.