This study analyzes the net energy output and optimum operating conditions for osmotic power generation from seawater brine based on the currently available hollow fiber membranes in the module scale. Factors that are influential on membrane performances, such as external concentration polarization, internal concentration polarization, salt reverse diffusion, and dilution have been taken into account. Net power density is defined and applied to characterize the efficiency of the PRO system, in terms of power production minus pumping energy, pretreatment cost and energy consumption by pressure drop in the membranes. When using 1 M NaCl as the draw solution and 10 mM NaCl as the feed, it is found that up to 7 W m(-2) net power density can be harvested by the PRO system depending on the water sources. Coupling with the existing RO plant is highly beneficial in terms of readily available high pressure source, high salinity and less or negligible pretreatment costs for the draw solution. Sources with higher salt concentrations are preferred. The optimum hydraulic pressure, module length, flow rate to membrane area ratio and feed to draw flow rate ratio have also been analyzed to maximize the net power output. In addition, implications on hollow fiber development are discussed. Fibers with high water permeability, lower structural parameter, good mechanical stability, better fouling resistance, and outer-selective configurations are recommended for further studies. (c) 2015 American Institute of Chemical Engineers AIChE J, 62: 1216-1225, 2016