Laboratory-scale experiments were conducted to determine optimum sludge residence time (SRT) and temperature of aerobic thermophilic pretreatment (ATP) of mixed sludge (thickened waste activated sludge and primary sludge) to achieve maximum pathogen reduction and best process performance. 4-L laboratory-scale ATP reactors were operated at SRTs of 0.6, 1.0, and 1.5 days and temperatures of 55, 58, 62, and 65°C. ATP at temperatures ≥62°C and SRT ≥0.6 day reduced the feed sludge fecal coliform density from 107 MPN/g total solids (TS) to 4 MPN/g TS. Salmonella in the feed sludge was reduced to <1 MPN/4 g TS from 2 to 18 MPN/4 g TS by ATP at temperatures ≥55°C and SRT ≥0.6 day. ATP was able to increase sludge volatile acids concentration by 100-200% over the feed sludge volatile acid concentration and to reduce sludge supernatant chemical oxygen demand from 20,000 to 22,000 mg/L in the feed to 13,000-17,000 mg/L in the ATP reactor. Volatile solids reduction by ATP increased from 25 to 40% when SRT was increased from 0.6 to 1.5 days, and a 5% increase in volatile solids reduction was seen at SRTs of 0.6, 1.0, and 1.5 days when ATP temperature was increased from 55 to 65°C.