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In this work, the techno-economic feasibility of a new process for biodiesel production from crude tall oil (CTO) was investigated. A solid acid-catalyzed (SAC) route based on esterification of free fatty acids (FFA) using a catalytic distillation column (CDC) with Relite CFS as the catalyst was employed. CTO purification was needed to achieve biodiesel standard specifications. A base case and an alternative process for CTO purification from four and three distillation columns were designed, optimized and techno-economically assessed. The alternative process was technically feasible for biodiesel production and also more economical and eco-friendly. Therefore, this process was investigated for biodiesel production by the SAC process using a CDC and a catalytic divided-wall column (CDWC). The CDWC process was not technically feasible, so that the CDC process was globally optimized based on six inputs. Finally, the effect of CTO composition was also investigated, so that a final design was obtained for biodiesel production using CTO coming from the United States of America, Canada and Scandinavia.