Ankle syndesmosis sprains are common injuries in collegiate and professional football. Several reports have documented that patients with syndesmosis injuries require a longer time to return to full athletic participation than patients with lateral ankle sprains. Here we present the cases of two professional football players with ankle pain secondary to syndesmosis ossification following documented syndesmosis ankle sprains. Both patients eventually required resection of the heterotopic ossification to allow a pain-free return to football. We conclude that syndesmosis ossification may be symptomatic in some patients, and surgical excision of the ossification may be required to allow an asymptomatic return to sports.