5-hydroxymethylfurfural (HMF) is a versatile renewable base chemical, which can be produced by the acid-catalyzed dehydration of fructose. At this time HMF cannot yet compete with oil-based analogues, such as p-xylene, due to the high costs of production. Future incentives to encourage the transition to a bio-based economy may increase the feasibility of investing in a HMF production process, but only if an efficient and cost-effective production method is designed. Previous research showed promising results using a reactive extraction unit. However, the selection of the organic solvent has a large influence on both the overall yield, as well as on the energy requirements in the final recovery of the HMF in a subsequent separation step. In this work, an intrinsically better, but hard to separate solvent, tri-butyl phosphate (TBP), was compared to methyl isobutyl ketone (MIBK), a solvent which is easy to separate from the HMF by distillation. The chosen method of separation for the TBP-HMF reaction mixture is back-extraction, using an anti-solvent to transfer the HMF back to an aqueous phase. By using backextraction, it was possible to lower the energy (steam) requirements of a TBP-based process under the benchmark calculated for a MIBK-based process by 18%. A drawback of the TBP-based process is its increased complexity, leading to higher capital costs. A model was developed to assess the balance between reduced steam demands and increased capital and operational costs. It was found that even if an optimistic scenario for the effectiveness of the anti-solvent was used, the MIBK-based process was superior across nearly all key performance indicators. Most indicative of the relative feasibility is the minimum selling price of HMF (at a production of 20 kton/year), which is €1.85/kg or €1.64/kg, for a TBP- and MIBK-based process respectively. The only area where the TBP-based process performs slightly better is sustainability, with calculated emissions of 1.90 kgCO2eq/kg HMF compared to 1.97 kgCO2eq/kg HMF for a MIBK-based process.