Particle-induced X-ray emission (PIXE) analysis is usually performed using proton beams with energies in the range 2∼3 MeV because at these energies, the detection limit is low. The detection limit of PIXE analysis depends on the X-ray production cross-section, the continuous background of the PIXE spectrum and the experimental parameters such as the beam currents and the solid angle and detector efficiency of X-ray detector. Though the continuous background increases as the projectile energy increases, the cross-section of the X-ray increases as well. Therefore, the detection limit of high energy proton PIXE is not expected to increase significantly. We calculated the cross sections of continuous X-rays produced in several bremsstrahlung processes and estimated the detection limit of a 20 MeV proton PIXE analysis by modelling the Compton tail of the γ-rays produced in the nuclear reactions, and the escape effect on the secondary electron bremsstrahlung. We found that the Compton tail does not affect the detection limit when a thin X-ray detector is used, but the secondary electron bremsstrahlung escape effect does have an impact. We also confirmed that the detection limit of the PIXE analysis, when used with 4 μm polyethylene backing film and an integrated beam current of 1 μC, is 0.4∼2.0 ppm for proton energies in the range 10∼30 MeV and elements with Z = 16–90. This result demonstrates the usefulness of several 10 MeV cyclotrons for performing PIXE analysis. Cyclotrons with these properties are currently installed in positron emission tomography (PET) centers.