AbstractThe oil industry needs to reduce CO2 emissions across the entire lifecycle of fossil fuels to meet environmental regulations and societal requirements and to sustain its business. With this goal in mind, this study aims to evaluate the CO2 mitigation potential of several bio‐oil co‐processing pathways in an oil refinery. Techno‐economic analysis was conducted on different pathways and their greenhouse gas (GHG) mitigation potentials were compared. Thirteen pathways with different bio‐oils, including vegetable oil (VO), fast pyrolysis oil (FPO), hydro‐deoxygenated oil (HDO), catalytic pyrolysis oil (CPO), hydrothermal liquefaction oil (HTLO), and Fischer–Tropsch fuels, were analyzed. However, no single pathway could be presented as the best option. This would depend on the criteria used and the target of the co‐processing route. The results obtained indicated that up to 15% of the fossil‐fuel output in the refinery could be replaced by biofuel without major changes in the core activities of the refinery. The consequent reduction in CO2 emissions varied from 33% to 84% when compared with pure equivalent fossil fuels replaced (i.e., gasoline and diesel). Meanwhile, the production costs varied from 17 to 31€/GJ (i.e., 118–213$/bbleq). Co‐processing with VO resulted in the lowest overall performance among the options that were evaluated while co‐processing HTLO in the hydrotreatment unit and FPO in the fluid catalytic cracking unit showed the highest potential for CO2 avoidance (69% of refinery CO2 emissions) and reduction in CO2 emissions (84% compared to fossil fuel), respectively. The cost of CO2 emissions avoided for all of the assessed routes was in the range of €99–651 per tCO2. © 2020 The Authors. Biofuels, Bioproducts, and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.