The orthogonal experiments of air gap membrane distillation (AGMD) with three factors and four levels were carried out to seek the best operation condition which considered the indexes of the permeation flux and the desalination rate. The effects of operating conditions, such as operating temperature, concentration of the NaCl solution, and feed flow rate on the indexes and desalination efficiency of the membrane were also investigated. It is shown, from the range and variance analyses of the experimental results, that the permeation flux is significantly affected by the operating temperature, but slightly affected by the concentration of the NaCl solution, and the permeation flux increases with the increasing operating temperature and feed flow rate. At the same time, the desalination rate is significantly affected by the operating temperature, but slightly affected by the feed flow rate, and the desalination rate decreases with the increasing operating temperature and the concentration. From all above, the conclusions could be following: the operating temperature must be determined as a proper value based on the balance between the energy consumption and the water throughput according to the practical conditions; the membrane prepared gets better desalination efficiency for 2% NaCl solution than the other concentration’s; the increase of the feed flow rate would result in the increasing permeation flux, which is benefit for the water throughput.