BACKGROUND Mixed martial arts (MMA) is a full combative sport with a recent global increase in popularity despite significant scrutiny from medical associations. To date, the empirical research of the risk of head injuries associated with this sport is limited. Youth and amateur participation is growing, warranting investigation into the burden and mechanism of injuries associated with this sport. PURPOSE (1) To determine the incidence, risk factors, and characteristics of knockouts (KOs) and technical knockouts (TKOs) from repetitive strikes in professional MMA; and (2) to identify the mechanisms of head trauma and the situational factors that lead to KOs and TKOs secondary to repetitive strikes through video analysis. STUDY DESIGN Descriptive epidemiology study. METHODS Competition data and video records for all KOs and TKOs from numbered Ultimate Fighting Championship MMA events (n = 844) between 2006 to 2012. Analyses included (1) multivariate logistic regression to investigate factors associated with an increased risk of sustaining a KO or TKO secondary to repetitive strikes and (2) video analysis of all KOs and TKOs secondary to repetitive strikes with descriptive statistics. RESULTS During the study period, the KO rate was 6.4 per 100 athlete-exposures (AEs) (12.7% of matches), and the rate of TKOs secondary to repetitive strikes was 9.5 per 100 AEs (19.1% of matches), for a combined incidence of match-ending head trauma of 15.9 per 100 AEs (31.9% of matches). Logistic regression identified that weight class, earlier time in a round, earlier round in a match, and older age were risk factors for both KOs and TKOs secondary to repetitive strikes. Match significance and previously sustained KOs or TKOs were also risk factors for KOs. Video analysis identified that all KOs were the result of direct impact to the head, most frequently a strike to the mandibular region (53.9%). The average time between the KO-strike and match stoppage was 3.5 seconds (range, 0-20 seconds), with losers sustaining an average of 2.6 additional strikes (range, 0-20 strikes) to the head. For TKOs secondary to strikes, in the 30-second interval immediately preceding match stoppage, losers sustained, on average, 18.5 strikes (range, 5-46 strikes), with 92.3% of these being strikes to the head. CONCLUSION Rates of KOs and TKOs in MMA are higher than previously reported rates in other combative and contact sports. Public health authorities and physicians should be cognizant of the rates and mechanisms of head trauma. Preventive measures to lessen the risks of head trauma for those who elect to participate in MMA are described.