The aim of this study was to evaluate the performance and digestate quality of advanced anaerobic digestion of sewage sludge including sequential ultrasound-thermal (55 degrees C) pre-treatment. Both stages of pre-treatment contributed to chemical oxygen demand (COD) solubilization, with an overall factor of 11.4 +/- 2.2%. Pretreatment led to 19.1, 24.0 and 29.9% increased methane yields at 30, 15 and 7.5 days solid retention times (SRT), respectively, without affecting process stability or accumulation of intermediates. Pre-treatment decreased up to 4.2% water recovery from the digestate, but SRT was a more relevant factor controlling dewatering. Advanced digestion showed 2.4-3.1 and 1.5 logarithmic removals of coliforms and coliphages, respectively, and up to a 58% increase in the concentration of inorganics in the digestate solids compared to conventional digestion. The COD balance of the process showed that the observed increase in methane production was proportional to the pre-treatment solubilization efficiency.