This paper evaluates the environmental and economic performance of liquefied natural gas (LNG) as a transition fuel to replace diesel in heavy goods vehicles (HGVs). A Well-to-Wheel (WTW) assessment based on real-world HGV drive cycles is performed to determine the life-cycle greenhouse gas (GHG) emissions associated with LNG relative to diesel. The analysis is complemented with a probabilistic approach to determine the total cost of ownership (TCO) across a range of scenarios. The methodologies are validated via a case study of vehicles operating in the UK, using data provided by a large food retailer. The spark-ignited LNG vehicles under study were observed to be 18% less energy efficient than their diesel counterparts, leading to a 7% increase in WTW GHG emissions. However, a reduction of up to 13% is feasible if LNG vehicles reach parity efficiency with diesel. Refuelling at publicly available stations enabled a 7% TCO saving in the nominal case, while development of private infrastructure incurred net costs. The findings of this study highlight that GHG emission reductions from LNG HGVs will only be realised if there are vehicle efficiency improvements, while the financial case for operators is positive only if a publicly accessible refuelling network is available.