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Introduction: Energy-based cosmetic devices offer an in-office treatment option, with minimal downtime, to non-invasively remove unwanted fat. We evaluated focused, pulsed ultrasound treatment to randomized flanks, compared to corresponding non-treated contralateral flanks., Material and Methods: Subjects were enrolled at three sites for a series of focused ultrasound treatments to a single flank, with the contralateral flank remaining untreated throughout the study. Success criteria included measureable fat thickness reduction on ultrasound imaging in the treated areas at 16 weeks after the final treatment session, and correct identification of the post-treatment photo and treated flank in at least 80% of evaluated images, as assessed by two blinded evaluators., Results: The post-treatment flank photo and treated flank side were correctly identified in 82% and 93% of cases, respectively. All study subjects demonstrated significant fat reduction in their treated area, as measured by ultrasound and skin caliper. Subjects expressed a high satisfaction from treatment outcomes. There were no complications with treatment., Conclusion: A series of three ultrasound treatments resulted in significant fat reduction in treated flanks. Although treatment results are more modest than with liposuction, non-invasive ultrasound treatment may provide an attractive alternative for patients seeking an in-office, nonsurgical procedure for fat reduction.