Anaerobic digestion (AD) is the most suitable approach for managing vinasse, the main wastewater from ethanol production, based on potential biogas applications. However, despite significant improvements in both scientific and technological aspects of the AD of vinasse, specific aspects of the global process require a better understanding to facilitate the scale-up of treatment systems. In this context, this study aimed to identify the main factors that affect the economic performance of the AD of vinasse in sugarcane biorefineries using a techno-economic approach. The energy recovery potential, as well as economic parameters were obtained for different biogas applications. Sensitivity analysis was also used to assess the impacts of different factors on the profitability of the process. Overall, biomethane production economically outperformed electricity generation, regardless of the biorefinery type (autonomous or annexed) and AD layout (single- or two-phase). In turn, investment costs on AD-power plants and product (electricity or biomethane) prices characterized the primary factors governing the economic performance of biogas reuse, regardless of the proposed application. These results confirm the key role of external agents in encouraging the implementation of AD plants in ethanol biorefineries by establishing specific funding for biogas projects, imposing environmental restrictions and/or developing competitive AD-related technological packages. (C) 2017 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.