The present study is a cradle-to-gate Life Cycle Assessment of a hypothetical production process of rigid polyurethane foam obtained from thistle seed oil, grown on the marginal soils of the Umbria region, Italy. Thistle is a particularly rustic crop, suitable for difficult soil and climatic conditions that allow its cultivation in the Mediterranean area on marginal lands and with only the water supply of the autumn-spring rains. Life Cycle Inventory was built on up-to-date inventory for thistle production, while experimental data for polyol and synthesis were obtained from literature, with reference to a pilot scale reactor. Energy recovery of lignocellulosic biomass and sensitivity analysis were also included in the study. Life Cycle Assessment was performed using SimaPro 9.0 and impacts were evaluated with the Impact2000+ method. Results show the overall impact of thistle oil including its final use for the production of polyurethane foam, and underline the important contribution as environmental benefit of the use of biomass leftovers in the agricultural phase. Moreover, results show that the major impacts of the rigid polyurethane foam production process were related to the synthesis of the foam itself. Among the previous phases constituting the process of synthesis of the polyol, the most impactful one was the cultivation; the oil processing stage, on the other hand, had a small global impact. The synthesis of the foam, taken individually, generated a greater impact than the entire synthesis process of the vegetable polyol starting from the cultivation of thistle.