Niobium- and tantalum-containing mesoporous molecular sieves MCM-41 have been synthesized, and applied as a catalyst for vapor phase Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam. NbMCM-41 catalyst exhibited high catalytic performance in the vapor phase Beckmann rearrangement of cyclohexanone oxime. The oxime conversions were almost 100% and the lactam selectivities were around 80%. The lactam selectivities of NbMCM-41 catalyst were higher than those of AlMCM-41 catalyst. However, TaMCM-41 catalyst exhibited lower catalytic performance than AlMCM-41 catalyst, and it was fast deactivated with time. These results may be due to the acidity difference among the catalysts. The results from NH3-TPD showed that NbMCM-41 catalyst possessed weak and medium acid sites, while TaMCM-41 catalyst possessed only very weak acid sites. AlMCM-41 catalyst also exhibited only weak acid sites.