Background: The most common ankle injury is the lateral ankle sprain. Dutch annual sports-related ankle sprain costs can roughly be estimated at 187,200,000. Research has shown that proprioceptive training accounts for an approximated overall 50% reduction in ankle sprain recurrence rate. Hypothesis: An unsupervised proprioceptive training program to reduce the recurrence of lateral ankle sprains will reduce overall health care costs. Design: Cohort study (economic analysis); Level of evidence, 2. Methods: The study included 522 male and female athletes: 256 athletes (120 female and 136 male) in the intervention group, and 266 athletes (128 female and 138 male) in the control group. Both groups received treatment according to usual care. Athletes allocated to the intervention group received an 8-week proprioceptive training program in addition to usual care. Costs per athlete and costs per injured athlete were calculated. Costs related to ankle sprain recurrences were measured from a societal perspective using cost diaries. Bootstrapping was used to analyze the cost-effectiveness data. Follow-up was 1 year. Results: Mean total costs in the intervention group were 81 (standard deviation, 134) per athlete and 114 (325) per injured athlete. Mean overall costs in the control group were 149 (836) per athlete and 447 (1403) per injured athlete. Statistically significant differences in total costs were found per athlete (mean difference, -69; 95% confidence interval, -200 to -2) and per injured athlete (-332; -741 to -62) in favor of the intervention group. A cost-effectiveness plane showed the effect of the intervention was larger and the costs were lower in the intervention group than the control group. Conclusion: The use of a proprioceptive training program after usual care of an ankle sprain is cost-effective for the prevention of ankle sprain recurrences in comparison with usual care alone. In the Netherlands, an estimated annual 35.9 million in medical and lost productivity costs can be saved solely by advocating a proprioceptive training program as in the present study. © 2010 The Author(s).