Membrane distillation (MD) can utilize low level thermal energy, such as waste heat and solar thermal heat, and holds high potential to replace conventional energetically intensive separation technologies. Two issues related to MD were investigated in this study by computational fluid dynamics (CFD) simulation. First, the trans-membrane mass fluxes are controlled by the heat transfer in the boundary layers adjacent to the membrane, but the applicability of conventional correlations developed for rigid heat exchangers on MD is questionable. Second, reported experimental study has shown that employing fluid channels with rough surface can enhance the performance of MD. However, the internal transfer characteristics of these modules have not been analyzed. This paper presents the results of the 3-D CFD simulation of the direct contact MD (DCMD) modules with and without rough surface channels for desalination. The simulation is comprehensive in that it covers the entire length of the module and takes into account the trans-membrane heat and mass transfer. The model was verified with reported experiment data and the average deviation of mass flux is less than 10%. The simulation results reveal that the thermal entrance effect, which gives very high mass flux and heat transfer coefficient, is significant for the simulated modules. The averaged heat transfer coefficients of the entire module are not close to the predictions from the conventional correlations. Hence, directly applying the conventional correlations of heat transfer coefficients to the MD modules is not appropriate.