This case study estimates the potential economic risk from permafrost thaw on oil and gas pipelines in the Russian Arctic as part of a larger effort to better understand complex interactions between human and natural systems in the Arctic. Pan-Arctic simulations of permafrost thaw-depth from the Community Land Model version 4.5 and ground ice characteristics were used to generate thaw-induced ground subsidence projections over the period 2020 to 2040 with a quantification of uncertainty. Engineering analysis and expert input were used to estimate the magnitude of ground subsidence likely to cause significant pipeline damage. Then, Russian oil and gas transmission pipeline networks were overlaid on the ground subsidence projections in ArcGIS to identify pipelines vulnerable to damage from permafrost thaw. Recent pipeline construction costs were used to estimate the total replacement costs for at-risk pipelines under several thaw scenarios. The results indicate that permafrost thaw poses a major threat to pipeline infrastructure, especially gas pipelines, in the Russian Arctic. Over the twenty-year study period, total replacement costs for oil and gas pipelines were estimated at $110 billion in 2020 USD. The study also includes an uncertainty analysis on the range of possible replacement cost estimates due to combined uncertainty from permafrost projections, pipelines’ subsidence tolerance, and Arctic construction costs. Reduced economic viability of pipelines under climate change could trigger major shifts in the Russian oil and gas industry, which would have impacts on global markets, emissions, and geopolitics.