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Abstract: The additional costs required for the pre‐treatment of lignocellulosic bio‐mass prior to enzymatic hydrolysis have limited the commercial implementation of lignocellulosic bio‐chemical production. The use of acidic mine drainage (AMD) water as an acid source for lignocellulosic pre‐treatment has recently been investigated. Large quantities of AMD in South Africa suggest that AMD can be obtained cheaply, thus reducing the cost and increasing the potential of lignocellulosic bio‐chemicals. Acidic mine drainage could undergo further remediation using sulfate‐reducing bacteria (SRB) so that the water is suitable for release. The feasibility of such a system could be greatly improved if this process were to be incorporated within a bio‐refinery, such that all fractions of the bio‐mass are used to produce multiple products. This paper investigates such a bio‐refinery system, and evaluates the different options based on the bio‐refinery complexity profile (BCP). Due to the abundance of grass in the regions where AMD is generated, this was found to be the most suitable feedstock. The most feasible bio‐refinery option was found to produce ethanol through fermentation of C6 sugars, although it is recommended that further investigation be conducted into additional high‐value bio‐chemicals from the C6 sugar platform. C5 sugars released in pre‐treatment could be used as a substrate by SRB for AMD remediation. Gasification and direct combustion of lignin had similar BCPs and thus further investigation is required to determine the preferred path. Similarly, further investigation is required for the best processing route for distillery silage. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]