Environmental reasons and circular economy opportunities have increased the interest in brine concentration technologies. The high thermal efficiency of vacuum-assisted air gap membrane distillation (V-AGMD) performed in multi-envelope modules with high residence time suggests that it could be a competitive technology for brine concentration. However, most of the studies so far are for seawater feeds, and the effect of feed salinity in the performance of V-AGMD at pilot scale has not been yet thoroughly assessed. This paper presents the first statistical model of the performance of a spiral-wound V-AGMD module in which feed salinity is included as a variable. Permeate flux and thermal efficiency are estimated as a function of evaporation and cooling inlet temperatures, feed flow rate and salinity. Accurate model equations have been developed and validated using experimental results obtained in a pilot-scale plant at the solar MD facilities of CIEMAT-PSA. This is the first assessment of pilot-scale MD which shows that from concentrations above 105.2 g L−1, the maximum thermal efficiency is obtained by increasing the feed flow rate, unlike at lower salinities. Moreover, for salinities above 140.3 g L−1 some operating conditions are not conducive to permeate production.