The new ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) approach has been proposed and shown to be successful in reproducing benchmark calculations and experimental results. ONIOM3, a three-layered version, divides a system into an active part treated at a very high level of ab initio molecular orbital theory like CCSD(T), a semiactive part that includes important electronic contributions and is treated at the HF or MP2 level, and a nonactive part that is handled using force field approaches. The three-layered scheme allows us to study a larger system more accurately than the previously proposed two-layered schemes IMOMO, which can treat a medium size system very accurately, and IMOMM, which can handle a very large system with modest accuracy. This three-layered scheme has been applied to activation barriers for the Diels-Alder reaction of acrolein + isoprene, acrolein + 2-tert-butyl-1,3-butadiene, and ethylene + 1,4-di-tert-butyl-1,3-butadiene. In general, the results for both geometry optimizations and single point energy calculations agree well with benchmark predictions and experimental results. The scheme has also been applied to the transition state for the oxidative addition of H-2 to Pt(P(t-Bu)(3))(2). The activation energy of this 83-atom reaction is predicted to be 14.2 kcal/mol with the ONIOM3(CCSD(T):MP2:MM3) method.