Vinasse is a by-product of sugarcane processing which is often used in fertigation; however, the direct use of vinasse harms the environment and reduces soil productivity due to its physicochemical properties. Anaerobic digestion (AD) offers an alternative to mitigate part of the negative effects. Anaerobic high-rate reactors, which mainly rely on sludge granulation, are mostly used in AD of vinasse wastewater. However, the composition of vinasse such as high concentration of solids and organic matter, high salinity, low pH, and high concentrations of sulfate, affect granule formation, leading to sludge washout. Anaerobic membrane bioreactors (AnMBR) present an alternative for vinasse treatment, eliminating the need for sludge granulation and producing a nutrient-rich effluent with minimal residual organics and no suspended solids. Research on sugarcane vinasse treatment using AnMBRs is limited. Most studies have employed submerged internal membrane modules, highlighting the need for further research with different reactor configurations to enhance process performance. In this study, an AnMBR equipped with an external inside-out crossflow ultrafiltration membrane was compared to an upflow anaerobic sludge blanket (UASB) reactor for the treatment of sugarcane vinasse. At a volumetric organic loading rate of up to 6 g COD. L-1.d-1, the UASB reactor reached 75% ± 7% of COD removal efficiency whereas the AnMBR generated a solids-free effluent and reached 88% ± 2% of COD removal efficiency. Microorganisms such as Clostridia, Bacteroidia, Mesotaga, Syner-01, Dehalococcoidia, Bacteroidia-DMER64, and Methanolinea were found as the most abundant. The results highlight the AnMBR potential as an effective alternative for treating sugarcane vinasse while overcoming the challenges posed by unsatisfactory sludge granulation.@en