Ünlü, G, Çevikol, C, and Melekoğlu, T. Comparison of the effects of eccentric, concentric, and eccentric-concentric isotonic resistance training at two velocities on strength and muscle hypertrophy. J Strength Cond Res 34(2): 337–344, 2020—The aim of this study was to compare the effects of concentric, eccentric, and eccentric-concentric isotonic resistance training at both fast and slow velocities to determine whether contraction modality affects muscle strength and hypertrophy. Forty-one young, healthy males (mean age 21.1 ± 1.8 years; height 178.9 ± 6.1 cm; body mass 70.5 ± 9.8 kg; and body mass index 22.0 ± 2.6 kg·m−2) were randomly assigned for 12 weeks to 1 of 5 resistance training groups to perform leg extension exercises 3 days a week (fast-eccentric; fast-concentric [FC]; slow-eccentric [SE]; slow-concentric; and concentric-eccentric [CE], 30°·s−1 for slow and 180°·s−1 for fast contractions), or to a nontraining control group (CG). Isotonic strength (1 repetition maximum [1RM]), isokinetic strength (peak torque), and quadriceps femoris muscle volume were measured before and after the 12 weeks of training program. In the early phase of the training period (first 3 weeks), the 1RM values of SE, FC, and CE increased remarkably (19.70, 13.73, and 19.35%, respectively; p < 0.05). Significant increases compared with the CG were found for muscle isotonic strength (∼25–41%, p < 0.001) and isokinetic peak torque at 60°·s−1 (∼13–32%, p < 0.05) in all training groups after the 12 weeks of the training period. No statistically significant interactions between the group and time were found on isokinetic peak torques at 180°·s−1 and muscle volume. Our results, therefore, suggest that all the training modalities in our study have the potential to induce isotonic strength gain in knee extensors, and there is insufficient evidence for the superiority of any specific mode of muscle contraction or velocity.