The physical origin of the open-circuit voltage in bulk heterojunction solar cells is still not well understood. While significant evidence exists to indicate that the open-circuit voltage is limited by the molecular orbital energies of the heterojunction components, it is clear that this picture is not sufficient to explain the significant variations which often occur between cells fabricated from the same heterojunction components. We present here an analysis of the variation in open-circuit voltage between 0.4–0.65 V observed for a range of P3HT/PCBM solar cells where device deposition conditions, electrode structure, active-layer thickness and device polarity are varied. The analysis quantifies non-geminate recombination losses of dissociated carriers in these cells, measured under device operating conditions. It is found that at open-circuit, losses due to non-geminate recombination are sufficiently large that other loss pathways may effectively be neglected. Variations in open-circuit voltage between different devices are shown to arise from differences in the rate coefficient for non-geminate recombination, and from differences in the charge densities in the photoactive layer of the device. The origin of these differences is discussed, particularly with regard to variations in film microstructure. By separately quantifying these differences in rate coefficient and charge density, and by application of a simple physical model based upon the assumption that open-circuit is reached when the flux of charge photogeneration is matched by the flux of non-geminate recombination, we are able to calculate correctly the open-circuit voltage for all the cells studied to within an accuracy of ±5 mV.