Sterczala, AJ, Flanagan, SD, Looney, DP, Hooper, DR, Szivak, TK, Comstock, BA, DuPont, WH, Martin, GJ, Volek, JS, Maresh, CM, and Kraemer, WJ. Similar hormonal stress and tissue damage in response to National Collegiate Athletic Association Division I football games played in two consecutive seasons. J Strength Cond Res 28(11): 3239–3243, 2014—The recovery process from a college football game has been studied, yet the stability of such findings year to year in the same players remains unclear. The purpose of this study was to examine the same players' biochemical recovery process in 2 consecutive seasons to a National Collegiate Athletic Association (NCAA) Division I football game. Ten starting players volunteered to participate in the study in each of the 2 seasons. Players performed a periodized heavy resistance training program over the entire year for each season. Fasted resting blood samples were obtained at similar times the Friday before the game (T1), 18–20 hours after the game (T2), and 42–44 hours after the game (T3). In both seasons, serum creatine kinase (CK) concentrations increased significantly from T1 to T2, and returned to T1 values at T3. When we compared seasons, CK values did not differ at any time point. Myoglobin demonstrated similar patterns and results. Testosterone and cortisol values were similar at all time points and did not differ by season as no significant differences were observed for the resting hormonal concentrations. The results of this study indicate that yearly programs should maintain a periodized progressive program, which seeks to increase physical potential of players while providing a protective effect on skeletal muscle and stabilization of hormonal status in response to both game and season stressors.