The purpose of this study was to evaluate the effects of altering the duration of the eccentric phase in isotonic contractions on muscle hypertrophy and strength of the quadriceps femoris. Ten healthy young adults (8 men and 2 women: Height: 173.3 ± 9.6 cm: Body mass: 69.84 ± 10.88 kg; Body fat: 19.47 ± 8.42%; Age: 25.3 ± 4.8 years) performed unilateral isotonic knee extension exercise, whereby each leg was randomly allocated to perform the eccentric phase of movement with a duration of either 2 seconds (G2S) or 4 seconds (G4S). Both conditions carried out the concentric phase of each repetition at a 1 second duration with no rest in the transition phases. Each condition performed 5 sets using 70% of 1 repetition maximum until muscle failure with 3 minutes of rest between sets for 8 weeks. The change in muscle strength was assessed by 1RM knee extension and muscle thickness was assessed by A-mode ultrasound. For each outcome variable, linear mixed-effects models were fit using restricted maximum likelihood. Hedges’ g effect sizes were calculated to provide insights into the magnitude of effects. Results showed all muscles increased in size over time; mean effects were similar in all muscles except for the vastus medialis, which favored the G4S condition. Conversely, only a trivial and highly variable effect was observed between interventions for strength gain. Our results suggest different eccentric durations produce similar increases in hypertrophy of the vastus lateralis and rectus femoris; however, the vastus medialis showed greater growth from the slower eccentric duration. Eccentric duration did not differentially affect strength-related adaptations.