Background: A previous report revealed an average of 7.2 (0.67 per 100,000 participants) sport-related structural brain injuries (SRSBIs) with macroscopic lesions per year in high school (HS) and college football players. The Lystedt law and other rule changes have been implemented with intent to reduce the risk of brain injury in football. Hypothesis: To update the profile of SRSBIs in HS and college football players and evaluate the efficacy of legislation intended to reduce brain injuries. Study Design: Descriptive epidemiology study. Level of Evidence: Level 4. Methods: We retrospectively reviewed 18 academic years (July 2002 through June 2020) of SRSBIs catalogued by the National Registry of Catastrophic Sports Injuries. The incidence of SRSBIs was assessed at the HS level during the pre (July 2002 through June 2009), transitional (July 2009 through June 2014), and post (July 2014 through June 2020) universal adoption time periods of the Lystedt law. In addition, the incidence of SRSBIs during the second half of the study (2011-2012 through 2019-2020) was compared with the first half of the study (2002-2003 through 2010-2011). Results: During the study period, there was a total of 228 SRSBIs (12.7 per year, 1.01 per 100,000 participants): 212 (93%, 11.8 per year, 1.00 per 100,000) in HS athletes and 16 (7%, 0.89 per year, 1.17 per 100,000) in college athletes. There were 52 fatalities (2.9 per year, 0.22 per 100,000 participants) with 46 (2.56 per year, 0.22 per 100,000) in HS athletes and 6 (0.33 per year, 0.43/100,000) in college athletes. There was no significant difference in risk of HS total SRSBIs or fatalities during the 3 Lystedt periods. The risk of combined SRSBI cases [relative risk (RR) = 1.22, P = 0.13] and fatalities (RR = 1.20, P = 0.52) was similar in the second half of the study compared with the first half of the study. Conclusion: Despite implementation of rule changes intended to reduce head injury, in particular the Lystedt law, the incidence of SRSBIs has remained unchanged. Further research is necessary to develop effective prevention programs for SRSBIs. Clinical Relevance: SRSBIs remain a persistent problem in HS and college American football. The recent head injury rule changes have not been effective at reducing SRSBIs.