Desalination of inland water resources such as brackish groundwater or geothermal water must achieve high water recovery to minimize reject brine volume and costs associated with its disposal. Pressure-driven membrane processes such as reverse osmosis (RO) and nanofiltration (NF) are presently the most commonly used technologies for desalination of brackish water; however, water recovery is often limited due to high scaling potential by silica, calcium, magnesium, and other minerals. Membrane distillation (MD), a thermally driven membrane process, is commonly tolerant to high salinity and may be less prone to irreversible fouling by mineral scaling. This investigation compared performance and fouling behavior of MD and NF during concentration of silica-containing solutions from 225 mg/L to 600 mg/L SiO2 at comparable operating conditions. Water flux was impacted by silica scaling in both MD and NF processes; however, an induction time was observed before flux decline occurred during MD experiments, which was not observed for NF. Salt rejection during MD was > 99.8% for all solutions tested and was unaffected by scaling, whereas rejection during NF was between 78% and 90% and tended to decrease after scaling. Attempts to clean the fouled membranes for both processes by rinsing with an NaOH solution at pH > 11 were partially effective at restoring water flux but unable to completely remove the silica scale layer.