We conducted a prospective trial at a military medical center to determine which treatment for first-time ankle sprains, early mobilization or immobilization, is more effective. Eighty-two patients with a lateral ankle sprain were randomly selected for one of two treatment groups. The Early Mobilization Group received an elastic wrap for 2 days followed by functional bracing for 8 days. Two days after injury, this group began weight-bearing and an ankle rehabilitation program. Patients in the Immobilization Group were placed in a nonweight-bearing plaster splint for 10 days followed by weight-bearing and the same rehabilitation program. Patients in the Early Mobilization Group had less pain at 3 weeks (57% versus 87%, P = 0.02); otherwise, there were no significant differences between groups in the frequency of residual symptoms. Only one patient in each group had residual symptoms 1 year after injury. Three patients (8%) in each group resprained their ankles. Ten days after injury, patients in the Early Mobilization Group were more likely to be back to full work (54% versus 13%, P < 0.001). We conclude that in first-time lateral ankle sprains, although both immobilization and early mobilization prevent late residual symptoms and ankle instability, early mobilization allows earlier return to work and may be more comfortable for patients.