The thermophilic and mesophilic digestion of instant-coffee-production wastewater in upflow anaerobic sludge blanket (UASB) reactors with thermophilic pre-acidification was studied over a period of more than 120 days. The UASB reactors had been seeded with granules adapted to this wastewater, and they previously operated in single-stage mode mesophilically or thermophilically. The thermophilic pre-acidification stage was operated with pH control or with 1.5 g 1-1 NaHCO3 added to the feed, at retention times of 24, 18, 15 and 12 h. Up to 38% of the total influent chemical oxygen demand (COD) was converted to total volatile fatty acids at a 24-h hydraulic retention time (HRT), dropping to 21% at a 12-h HRT. It was found that control with NaOH to pH 6.0 at an HRT of 24 h was not required for efficient acidogenesis. The effluent from the acidogenic stage at pH 5.2 did not require prior neutralisation with NaOH before feeding to the methanogenic stage. The absence of neutralisation improved the performance of the thermophilic UASB reactor. Thermophilic digestion may be more sensitive to Na+ toxicity than mesophilic digestion. The thermophilic/mesophilic two-stage system gave a consistent improvement in performance (measured, for example, as % COD reduction) over the thermophilic/thermophilic two-stage system, especially at higher organic loading rates. Thermophilic pre-acidification gave an increase of 60% in the loading rate achievable with the mesophilic methanogenic stage (a 100% reduction in HRT) compared with the single-stage system.