The results of a comparative analysis of three potential river port sites and associated road networks to support mineral development activity in western Alaska are reported in this paper. A 50,000-square-mile area of western Alaska bounded by the Yukon and Kuskokwim rivers is experiencing accelerated mineral exploration and mining activity. One potential project, with 11 million ounces of drill measured and indicated gold resources and 16 million ounces of drill inferred gold resources would require annual delivery of between 240,000 and 470,000 tons of fuel and equipment. Geologists estimate that an additional 17 million ounces are likely to be discovered within the study area during the next 25 years. Three potential river port locations and associated road corridors that could support anticipated, large-scale mining operations within the study area evaluated using a benefit-cost study approach. Two of the port and road corridor options generate estimated net present benefit values that exceeded estimated net present cost values. The port and road corridor option with the highest positive net present benefit value may not provide sufficient capacity to meet the area’s logistical requirements, and two ports may be built to support anticipated mineral development activities.