Thermophilic bacteria and spores along can survive milk pasteurization and reduce its shelf life. Milk quality is altered by enzymes produced by surviving microbes in milk. Coupling thermosonication with pasteurization may reduce the microbial load and enhance the product shelf life. This study evaluated the effect of flow through thermosonication using a plate heat exchanger and sonicator source (Heischler UIP500hd, Ringwood, NJ) on the survival of thermophilic and indigenous organisms in milk. For the thermophilic study, sterile 2% fat milk was inoculated with Geobacillus stearothermophilus (GS) and for indigenous microflora, raw milk was used (initial microbial count for both were 10⁴ to 10⁵ cfu/mL). Milk inoculated with GS and raw milk were treated with either heat (control) or heat and thermosonication (treatment) at 72°C at settings 1, 2, and 3 and settings 1 and 2, respectively that resulted in different heat (15.8, 13.2, and 12.1 s) and thermosonication (18.8, 12.8. and 8.1 s) times. Heat treatment before thermosonication of GS inoculated milk resulted in significant log reductions (P-values: 0.04, 0.04, 0.0005) of 0.45 ± 0.04, 0.26 ± 0.07, and 0.15 ± 0.01, at setting 1, 2, and 3, respectively; for heat treatment after thermosonication, significant log reductions (P-values: 0.02, 0.03, 0.0004) were seen at setting 1, 2, and 3 (0.54 ± 0.08, 0.35 ± 0.03, and 0.08 ± 0.01). Heat treatment reduced the cfu/mL of GS (log reduction ranging between 0.018 and 0.368 at all settings); but the reduction was not significant (P-values >0.05). The position of the sonicator did not have a significant effect (P-value = 0.95) on GS reductions. For raw milk, heat alone resulted in significantly lower log reductions (P-values: 0.005 and 0.02) (1.43 ± 0.03 and 0.69 ± 0.05) as compared with heat along with sonication (1.97 ± 0.14 and 1.14 ± 0.15) for setting 1 and 2, respectively. The shelf life was 5 weeks for setting 1 and 3 weeks for setting 2. Sonication along with heat treatment resulted in significantly higher log reductions for inoculated thermophilic bacteria and inherent microflora in milk as compared with heat alone. Use of pasteurization along with thermosonication may potentially reduce the microbial load of in milk leading to products with extended shelf life.