Performance of a series of eccentric contractions produces adverse effects including muscle weakness, delayed onset muscle soreness (DOMS), fluid accumulation and decreased muscle function. The repeated bout effect is a physiological adaptation observed when a single-bout of eccentric exercise protects against muscle damage from subsequent eccentric bouts. Similar to the repeated bout effect, increases in flexibility have been linked to attenuations in acute muscle damage, muscle fatigue and strength loss after eccentric exercise. Purpose: The purpose of this study was to examine the muscle physiological responses to eccentric strength training after first priming the muscles with either a period of static flexibility training or a single intense bout of eccentric exercise performed weeks earlier; and compare these to the responses from eccentric strength training when no prior intervention is administered. Methods: Twenty-five participants were randomly assigned to a flexibility (F) (n=8), a single-bout (SB) (n=9), or a control (C) (n=8) group. The design consisted of two 4-week phases; 1) priming intervention, 2) eccentric training. The priming intervention included static stretching (3x/week; 30mins/day) (F), a single-bout of eccentric exercise (SB) or no priming intervention (C). All groups proceeded to complete eccentric training of the knee flexors using isotonic contractions (%load progressively increased over training period) on a dynamometer following the priming intervention phase. Testing was completed at baseline, post-priming intervention and post-eccentric training, in conjunction with data being collected during the acute eccentric training phase (0hr, 24hr, 48hr; post-bout 1 and 4). Dependent measures included muscle thickness, isometric maximal voluntary contraction (MVC), eccentric and concentric MVC, optimal angle, active range of motion (ROM), passive ROM, maximal power, electromyography (EMG) and delayed onset muscle soreness (DOMS). Results: Acute data during the eccentric training phase revealed a significant reduction in DOMS for both the F and SB groups compared to the C following the first bout of eccentric exercise (p<0.05). The F also had reduced soreness in comparison to both the SB and C post fourth bout of eccentric exercise (p<0.05). The F group demonstrated attenuated loss in isometric strength (post fourth bout) and maximal power (post first bout) during eccentric training compared to the C group (p<0.05). However, there was no significant difference between groups across all dependent variables following the eccentric training phase. Conclusion: This is the first study to directly compare the protective effects observed with static flexibility training to that of a single-bout of eccentric exercise throughout a subsequent eccentric training regime. Although differences in muscle soreness, strength and maximal power occurred during the acute stages of eccentric training, there appeared to be no significant advantage of either protective priming method at the end of eccentric training.