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We analysed the effects of an experimental novel protocol of intensive hydrotherapy with hydrogen-rich water (HRW) on injury recovery in athletic men who suffered an acute ankle sprain (AAS) and compared it with a RICE protocol (rest, ice, compression, elevation). Professional athletes (age 23.7 ± 4.0 years; weight 78.6 ± 5.7 kg, height 182.5 ± 4.3 cm; professional experience 5.9 ± 3.9 years) who incurred AAS during a sport-related activity were randomly assigned immediately after the injury to either hydrogen group (n = 9) or a conventional RICE treatment group (n = 9). Hydrogen group received six 30-min ankle baths with HRW throughout the first 24 h post-injury, with hydrotherapy administered every 4 hours during the intervention period. RICE group stood off the injured leg, with ice packs administered for 20 min every 3 hours, with the injured ankle compressed with an elastic bandage for 24 hours and elevated at all possible times above the level of the heart. HRW was equivalent to RICE protocol to reduce ankle swelling (2.1 ± 0.9% vs. 1.6 ± 0.8%; P = 0.26), range of motion (2.4 ± 1.3 cm vs. 2.7 ± 0.8 cm; P = 0.60), and single-leg balance with eyes opened (18.4 ± 8.2 sec vs. 10.7 ± 8.0 sec; P = 0.06) and closed (5.6 ± 8.4 sec vs. 3.9 ± 4.2 sec; P = 0.59). This non-inferiority pilot trial supports the use of HRW as an effective choice in AAS management. However, more studies are needed to corroborate these findings in other soft tissue injuries. [ABSTRACT FROM AUTHOR]