Objective A rapid method was constructed for detection of 3 kinds of phosphodiesterase 5 (PDE5) inhibitors (sidenafil, vardalafil, tadalafil) in invigorative health food by paper spray ionization mass spectrometry (PSI-MS method). Methods The characteristic ions of the PDE5 inhibitors could be used for preliminary identification and semiquantitative analysis with internal standard method using PSI-MS method. Results The 24 kinds of commercially available health-care products includes capsule, tablet, pill, powder, wine, syrup and liquid were tested. Results from PSI-MS were consistent with the HPLC-UV date. The calibration curves of PSI-MS has a good linearity in a given range. The linear coefficients of analytes were higher than 0.99. The LODs of 3 kinds of PDE5 inhibitors were lower than 1.0 mg/L. The RSDs of this method ranged from 20% to 24%. Conclusion The PSI-MS method was rapid, accurate and targeted, which is compliant for quickly screening the PDE5 inhibitors in large complex matrix samples.