To investigate the effect of different drying methods on the ultra high performance liquid chromatography(UPLC) and physical fingerprint of the extract powder of Maimendong Decoction.Methods:Spray drying，vacuum drying，blast drying，and freeze drying were used to prepare the extract powder of Maimendong Decoction.The UPLC fingerprint was established，and the physical fingerprint was constructed with 5 first-level indicators and 9 second-level indicators.Similarity evaluation，cluster analysis，and principal component analysis were performed to compare the differences between UPLC fingerprint and physical fingerprint.The compressibility parameters were calculated to compare the compressibility of the four extract powders of Maimendong Decoction.Results:The UPLC fingerprints of the four extract powders of Maimendong Decoction had the similarity all greater than 0.95，and the similarities of physical fingerprint were 0.955，0.888，0.987，and 0.941，respectively.The cluster analysis of UPLC fingerprint and physical fingerprint were both consistent，which divided the four extract powders of Maimendong Decoction into two categories，and three and two principal components were obtained from the principal component analysis，respectively，which contained 100% and 90.03% of the original data，respectively.The spray-dried powder had the optimal compressibility.Conclusion:Different drying methods had little effect on the UPLC fingerprint of the extract powder of Maimendong Decoction，but exerted a significant effect on its physical fingerprint.