The anaerobic degradation of 2-propanol, an important industrial solvent, was scaled-up from batch assays to a pilot expanded granular sludge bed (EGSB) reactor at 25 °C. Batch studies indicated that 2-propanol followed Haldane kinetics, with a maximum rate at 10 g COD L−1. Concentrations as high as 25 g COD L−1 did not inhibit the degradation of ethanol, a common co-solvent. Similar specific methanogenic activities (SMA) were obtained for water-solvent and water-brewery sludges (88 and 77 ml CH4 g-VS−1 d−1 at 5 g COD L−1). Continuous degradation showed a lag-phase of three weeks with water-brewery sludge. Increases in 2-propanol load from 0.05 to 0.18 kg COD kg-VS−1 d−1 caused a shift from the consumption of soluble matter to methane production, indicating polyhydroxybutyrates (PHB) accumulation. Conversely, smooth increases of up to 0.29 kg COD kg-VS−1 d−1 allowed 2-propanol degradation without PHB accumulation. The slowdown rate of 2-propanol-oxidizer and acetate-utilizing methanogen bacteria below 20 °C adversely impacted both removal and CH4 yield.