BACKGROUND The use of cryotherapy in the management of acute soft tissue injury is largely based on anecdotal evidence. Preliminary evidence suggests that intermittent cryotherapy applications are most effective at reducing tissue temperature to optimal therapeutic levels. However, its efficacy in treating injured human subjects is not yet known. OBJECTIVE To compare the efficacy of an intermittent cryotherapy treatment protocol with a standard cryotherapy treatment protocol in the management of acute ankle sprains. METHODS Sportsmen (n = 44) and members of the general public (n = 45) with mild/moderate acute ankle sprains. METHODS Subjects were randomly allocated, under strictly controlled double blind conditions, to one of two treatment groups: standard ice application (n = 46) or intermittent ice application (n = 43). The mode of cryotherapy was standardised across groups and consisted of melting iced water (0 degrees C) in a standardised pack. Function, pain, and swelling were recorded at baseline and one, two, three, four, and six weeks after injury. RESULTS Subjects treated with the intermittent protocol had significantly (p<0.05) less ankle pain on activity than those using a standard 20 minute protocol; however, one week after ankle injury, there were no significant differences between groups in terms of function, swelling, or pain at rest. CONCLUSIONS Intermittent applications may enhance the therapeutic effect of ice in pain relief after acute soft tissue injury.