Objectives: The incidence of concussions in football, and the media attention that followed, has garnered scientific investigation, prompted technological advances in protective gear, and altered the rules of the game, including the NFL’s “Targeting” rule, which began in 2018. In previously studied seasons, certain positions, such as offensive skill players, had higher rates of concussions while defensive secondary and offensive line players suffered the greatest number of concussions, but the severity of these concussions has not been reported. The advent of the “Targeting” rule has been shown to reduce concussions in collegiate football leagues, but its effect on NFL and professional-level players is unknown. The objectives of this retrospective study were to describe the epidemiology of concussions among professional football players in the NFL during the last five seasons, determine changes in incidence over the study period, and characterize positional differences in rate and games missed. Methods: The current study was a descriptive epidemiological study that retrospectively reviewed all concussions that occurred in the five NFL seasons from the 2017-2018 season through the 2021-2022 season that resulted in at least one game missed. Total concussions, total games missed due to concussion, and average games missed per concussion were extracted from publicly available injury reports and were cross-referenced with publicly available sources. Concussion rates were calculated per 1,000 athletic exposures (AEs). A sub-analysis was performed by year, game unit, position type, and game week. Results: In 1,216 regular season games in the five NFL seasons, there were a total of 368 concussions for a rate of 0.30 concussions per game and 7.04 concussions per 1,000 AEs. More concussions were concentrated in the last one-third of the regular season. There was a statically significant decrease (38%; p<0.05) in total concussions between the 2017-2018 season (102 total concussions) and the four seasons between 2018-2019 and 2021-2022 (average of 73.8 concussions per year). During the five seasons, there were 1,014 games missed due to concussion, an average of 2.76 games missed per concussion, and 0.056 games missed due to concussion per 1,000 AEs. Following the 2017-2018 season, there was a 53% decrease in the total games missed due to concussion (Figure 1b) and a 38% decrease in the average games missed per concussion (Figure 1c). Descriptively, both offensive and defensive units had decreased concussion rates and average games missed per concussion in the four seasons after 2017 (Figure 2). Defensive backs (10.46 per 1,000 AEs) and tight ends (10.69 per 1,000 AEs) had the highest concussion rates. The defensive line had the highest average games missed per concussion at 3.97 (Table 1). Conclusions: The introduction of the “Targeting” rule in the NFL beginning in the 2018 season correlated with a decrease in total concussions per year, total games missed per concussion, and games missed per concussion. Both offensive and defensive units experienced similar reductions in concussion incidence and severity. Overall, the updated epidemiology of NFL concussions suggests that efforts to protect professional football players from concussions have been successful, however, players continue to experience concussions that require them to miss multiple games. [Table: see text]