Eccentric quasi-isometric (EQI) contractions have been proposed as a novel training method for safely exposing the musculotendinous system to a large mechanical load/impulse, with few repetitions. However, understanding of this contraction type is rudimentary. We aimed to compare the acute effects of a single session of isotonic EQIs with isokinetic eccentric (ECC) contractions. Fifteen well-trained men performed a session of impulse-equated EQI and ECC knee extensions, with each limb randomly allocated to one contraction type. Immediately PRE, POST, 24/48/72h, and 7days post-exercise, regional soreness, quadriceps swelling, architecture, and echo intensity were evaluated. Peak concentric and isometric torque, rate of torque development (RTD), and angle-specific impulse were evaluated at each time point. There were substantial differences in the number of contractions (ECC: 100.8 ± 54; EQI: 3.85 ± 1.1) and peak torque (mean: ECC: 215 ± 54 Nm; EQI: 179 ± 28.5 Nm). Both conditions elicited similar responses in 21/53 evaluated variables. EQIs resulted in greater vastus intermedius swelling (7.1-8.8%, ES = 0.20-0.29), whereas ECC resulted in greater soreness at the distal and middle vastus lateralis and distal rectus femoris (16.5-30.4%, ES = 0.32-0.54) and larger echogenicity increases at the distal rectus femoris and lateral vastus intermedius (11.9-15.1%, ES = 0.26--0.54). Furthermore, ECC led to larger reductions in concentric (8.3-19.7%, ES = 0.45-0.62) and isometric (6.3-32.3%, ES = 0.18-0.70) torque and RTD at medium-long muscle lengths. A single session of EQIs resulted in less soreness and smaller reductions in peak torque and RTD versus impulse-equated ECC contractions, yet morphological shifts were largely similar. Long-term morphological, architectural, and neuromuscular adaptations to EQI training requires investigation.