BACKGROUND Vacuum applicators have been effective for cryolipolysis of the abdomen, flanks, inner thighs, back, chest, and arms. However, the lateral thighs have not been easily treated because fat from this area cannot be easily drawn into a vacuum cup. OBJECTIVE The authors investigated the safety and efficacy of a prototype applicator for treatment of "nonpinchable" fat in the lateral thighs. METHODS In this prospective, nonrandomized, interventional cohort, multicenter study, a 120-minute unilateral treatment with a prototype conformable-surface applicator was performed on 1 lateral thigh of 40 patients, with the contralateral thigh serving as the control. During follow-up visits at 2 and 4 months, fat reduction was assessed by ultrasound imaging and clinical photography, and patient satisfaction surveys were completed. RESULTS Ultrasound data indicated a 2.6-mm mean normalized reduction in fat thickness-a statistically significant reduction vs the untreated control thigh (P = 7.8E-8). According to patient survey responses, 89% of patients would recommend the procedure to a friend; 86% were satisfied with cryolipolysis for the lateral thighs; 86% noticed visible fat reduction; and 97% were likely to undergo a second treatment. A panel of 3 independent blinded physicians correctly identified baseline and posttreatment clinical photographs in 87% of cases. There were no serious adverse events or unanticipated adverse device effects. CONCLUSIONS The cryolipolysis conformable-surface applicator was safe and efficacious for treatment of lateral thigh fat. Clinical photographs and ultrasound results showed significant reduction in fat thickness, and noticeable reduction in undesirable "saddlebag" bulges. LEVEL OF EVIDENCE 3: Therapeutic.