Twenty subjects were randomly assigned to: 1) prophylactic ibuprofen (N = 5) [400 mg TID initiated 4 h before collection of baseline data and strenuous eccentric exercise bout], 2) therapeutic ibuprofen (N = 5) [400 mg TID initiated 24 h after baseline], 3) placebo (N = 5), or 4) control (N = 5). Muscle soreness perception, plasma creatine kinase, knee extensor torque, and EMG of the quadriceps were evaluated at baseline, 24, and 48 h. The prophylactic ibuprofen group had between 40 and 50% less muscle soreness perception and significantly less decline in isometric, concentric, and eccentric torque at 24 h compared with the other three groups (P < 0.05). At 48 h both prophylactic and therapeutic ibuprofen had significantly less muscle soreness perception and decline in torque than the placebo and control groups (P < 0.05). There was no difference between the amount of muscle damage between the four groups at 24 and 48 h. Vastus medialis and lateralis EMG magnitude decreased across time. Vastus lateralis EMG magnitude had significantly less decline from baseline for prophylactic ibuprofen compared with the other three treatments at 24 h, while both prophylactic and therapeutic ibuprofen had significantly less decline at 48 h. These data indicate that a prophylactic dosage of ibuprofen does not prevent CK release from muscle, but does decrease muscle soreness perception and may assist in restoring muscle function.