Phase separation in molecular donor-acceptor mixtures composed of pentacene and C-60 is examined using a combination of computational and experimental methods. Classical molecular dynamics simulations of the relaxation process of pentacene:C-60 mixtures predict the formation of pentacene stacks and C-60 clusters in the equilibrated structures. These findings are consistent with experimental observations, where x-ray diffraction and atomic force microscopy characterization of the mixed films confirm the existence of polycrystalline pentacene domains. The scanning electron and atomic force micrographs of mixed films deposited at different rates as well as with various mixing ratios show that the aggregation of pentacene, and therefore the degree of phase separation in the mixtures, can be manipulated by the processing conditions. Finally, bulk heterojunction photovoltaic devices using different pentacene:C-60 mixtures as an active layer are fabricated and their photovoltaic performance characteristics are compared. It is found that the device with 1:5.5 (by weight) mixing ratio of pentacene:C-60 shows nearly 400 times higher power conversion efficiency than the 1:1 device due to successful control of nanoscale phase separation that leads to better exciton diffusion and charge collection. (C) 2009 American Vacuum Society. [DOI: 10.1116/1.3072516]