Loss mechanisms responsible for the sudden depletions of the outer electron radiation belt are examined based on observations and radial diffusion modeling, with L*-derived boundary conditions. SAMPEX data for October–December 2003 indicate that depletions often occur when the magnetopause is compressed and geomagnetic activity is high, consistent with outward radial diffusion for L* > 4 driven by loss to the magnetopause. Multichannel Highly Elliptical Orbit (HEO) satellite observations show that depletions at higher L occur at energies as low as a few hundred keV, which excludes the possibility of the electromagnetic ion cyclotron (EMIC) wave-driven pitch angle scattering and loss to the atmosphere at L* > 4. We further examine the viability of the outward radial diffusion loss by comparing CRRES observations with radial diffusion model simulations. Model-data comparison shows that nonadiabatic flux dropouts near geosynchronous orbit can be effectively propagated by the outward radial diffusion to L* = 4 and can account for the main phase depletions of outer radiation belt electron fluxes.