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In the present study, the effect of thermosonication on polyphenol oxidase (PPO) inactivation and quality parameters of soursop nectar was evaluated [at 24 kHz, average temperature of 34, 44 and 54 °C, acoustic energy density (AED) (1.1, 1.2 and 1.4 W/mL) and processing time (2, 6 and 10 min)]. Classical thermal pasteurization (65 °C, 30 min) reduced 81% PPO activity and ascorbic acid content by 36% in comparison to fresh nectar. All treatments with thermosonication at 34 or 44 °C decreased the initial PPO activity between 34 and 67%; while treatments at 54 °C decrease PPO activity among 91 and 99%. Also these last treatments had 90% retention of ascorbic acid, without significant changes in quality parameters. In conclusion, thermosonication can be an excellent alternative to total PPO inactivation, without changes in the quality of soursop nectar.