Because of the problems with sludge formation and inability to meet water reuse standards with traditional limestone neutralization, nanofiltration (NF) has been evaluated for treatment of abandoned mine drainage (AMD). This study contributes to the process of selecting NF membranes based on laboratory-scale studies that is validated in pilot-scale system with real AMD under relevant process conditions to recover: (1) treated water stream (NF permeate) that can serve as a substitute for fresh water in industrial applications and (2) concentrated sulfate stream (NF reject) that is well-suited to control divalent cations in the produced water from unconventional gas extraction by sulfate precipitation and enable its reuse for hydraulic fracturing of subsequent wells. Eight commercially available NF membranes were tested with synthetic and real AMD in laboratory-scale dead-end and cross-flow membrane filtration modules. NF90 membrane was selected for pilot-scale study that consisted of aeration and sedimentation for iron control, bag filtration and ultrafiltration for particulate control and NF. The system was operated for 208 h using real AMD at 10 bar and 3.5 GPM feed flow rate and consistently achieved more than 98% removal of TDS at 57% water recovery with a nominal pressure drop of 1.7 bar. Pressure drop monitoring and water permeability tests post pilot-scale study along with chemical equilibrium calculations indicated that no fouling/scaling of the membranes occurred.