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Background: Acute lateral ankle sprains are common injuries among athletes, but the optimal treatment strategies in elite athletes are still debated. This proof-of-concept study aimed to assess the impact of cryo-ultrasound therapy on the short-term recovery of football players with acute lateral ankle sprains. Methods: Semi-professional football players with grade I or II lateral ankle sprains were randomly assigned to the experimental group (receiving cryo-ultrasound therapy combined with conventional physical therapy) or control group (sham cryo-ultrasound therapy combined with conventional physical therapy). Pain intensity and physical functioning were assessed by the Numeric Rating Scale (NRS) and Foot and Ankle Disability Index (FADI) at baseline (T0) at the end of treatment (T1), after one month (T2), and two months after treatment (T3). Results: After the study intervention, significant between groups differences were reported in terms of pain relief (NRS: 4.08 ± 1.29 vs. 5.87 ± 1.19; p = 0.003) and physical function (FADI: 50.9 ± 10.3 vs. 38.3 ± 11.5; p = 0.021). However, no significant between group differences were reported at T2 and T3. No adverse effects were reported. Conclusions: Cryo-ultrasound therapy combined with conventional physical therapy can accelerate recovery and early return to sport in elite football players with acute lateral ankle sprains. While this study contributes valuable insights into the potential benefits of cryo-ultrasound therapy, further investigations with a longer follow-up are needed to validate and optimize the application of physical agent modalities in the management of ankle injuries.