Groundwater brine seepage into the Dolores River in Paradox Valley, Colorado, increases the dissolved solids load of the Colorado River annually by ∼2.0 × 10⁸ kg. To abate this natural contamination, the Bureau of Reclamation plans to pump ∼3540 m³/d of brine from 12 shallow wells located along the Dolores River. The brine, with a salinity of 250,000 mg/L, will be piped to the deepest (4.9 km) disposal well in the world and injected mainly into the Mississippian Leadville Limestone. Geochemical modeling indicates, and water-rock experiments confirm, that a huge mass of anhydrite (∼1.0 × 10⁴ kg/d) likely will precipitate from the injected brine at downhole conditions of 120°C and 500 bars. Anhydrite precipitation could increase by up to 3 times if the injected brine is allowed to mix with the highly incompatible formation water of the Leadville Limestone and if the Mg in this brine dolomitizes the calcite of the aquifer. Laboratory experiments demonstrate that nanofiltration membranes, which are selective to divalent anions, provide a new technology that remediates the precipitation problem by removing ∼98% of dissolved SO₄ from the hypersaline brine. The fluid pressure used (50 bars) is much lower than would be required for traditional reverse osmosis membranes because nanofiltration membranes have a low rejection efficiency (5–10%) for monovalent anions. Our results indicate that the proportion of treatable brine increases from ∼60% to >85% with the addition of trace concentrations of a precipitation inhibitor and by blending the raw brine with the effluent stream.