The stability considerations of centrifugal compressors become increasingly severe with the high pressure ratios, especially in aero-engines. Diffuser is the major subcomponent of centrifugal compressor, and its performance greatly influences the stability of compressor. This paper experimentally investigates the roles of vanes in diffuser on component instability and compression system instability. High pressure ratio centrifugal compressors with and without vanes in diffuser are tested and analyzed. Rig tests are carried out to obtain the compressor performance map. Dynamic pressure measurements and relevant Fourier analysis are performed to identify complex instability phenomena in the time domain and frequency domain, including rotating instability, stall, and surge. For component instability, vanes in diffuser are capable of suppressing the emergence of rotating stall in the diffuser at full speeds, but barely affect the characteristics of rotating instability in the impeller at low and middle speeds. For compression system instability, it is shown that the use of vanes in diffuser can effectively postpone the occurrence of compression system surge at full speeds. According to the experimental results and the one-dimensional flow theory, vanes in diffuser turn the diffuser pressure rise slope more negative and thus improve the stability of compressor stage, which means lower surge mass flow rate.