An increased incidence of amyotrophic lateral sclerosis (ALS) amongst soccer players in Italy has recently been reported. A case-control study (300 cases and 300 matched controls) was conducted to explore the association between ALS and physical/sports activities, with specific reference to trauma-related risk. Neither the practice of competitive sports nor sports-related traumas were found to be associated with an increased risk of ALS. The practice of physical activities or sports is not per se a risk factor for ALS. Our results exclude sports-related microtraumas as etiopathogenic factors in the natural history of ALS.