The Delaware River has made a marked recovery in the half-century since the adoption of the Delaware River Basin Commission (DRBC) Compact in 1961 and passage of the Federal Clean Water Act amendments during the 1970s. During the 1960s, the DRBC set a 3.5 mg/L dissolved oxygen criterion for the river based on an economic analysis that concluded that a waste load abatement program designed to meet fishable water quality goals would generate significant recreational and environmental benefits. Scientists with the Delaware Estuary Program have recently called for raising the 1960s dissolved oxygen criterion along the Delaware River from 3.5 mg/L to 5.0 mg/L to protect anadromous American shad and Atlantic sturgeon, and address the prospect of rising temperatures, sea levels, and salinity in the estuary. This research concludes, through a nitrogen marginal abatement cost (MAC) analysis, that it would be cost-effective to raise dissolved oxygen levels to meet a more stringent standard by prioritizing agricultural conservation and some wastewater treatment investments in the Delaware River watershed to remove 90% of the nitrogen load by 13.6 million kg N/year (30 million lb N/year) for just 35% ($160 million) of the $449 million total cost. The annual least cost to reduce nitrogen loads and raise dissolved oxygen levels to meet more stringent water quality standards in the Delaware River totals $45 million for atmospheric NOX reduction, $130 million for wastewater treatment, $132 million for agriculture conservation, and $141 million for urban stormwater retrofitting. This 21st century least cost analysis estimates that an annual investment of $50 million is needed to reduce pollutant loads in the Delaware River to raise dissolved oxygen levels to 4.0 mg/L, $150 million is needed for dissolved oxygen levels to reach 4.5 mg/L, and $449 million is needed for dissolved oxygen levels to reach 5.0 mg/L.