Background <p>Accentuated eccentric loading (AEL) may acutely enhance the concentric (CON) barbell velocity after the additional eccentric (ECC) load is removed, however there are inconsistent results regarding the effectiveness of this practice within the scientific literature.</p> Objective <p>The aims of the present study were to: (1) examine the acute effects of applying AEL, only on the first repetition of a set, on mean barbell velocity during the CON phase of the first 3 repetitions of the set and (2) investigate the influence of the magnitude of ECC load, loading differential and exercise selection on the acute effects of AEL.</p> Methods <p>Four databases (PubMed, Web of Science, SPORTDiscus, and Google Scholar) were searched for peer-reviewed literature. Eligible studies included those that applied a greater external load during the ECC phase than during the CON phase in free-weight resistance training in an injury-free, strength-trained population. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials (RoB 2) adapted for crossover trials. The outcome of interest was the mean barbell CON velocity across the first three repetitions, comparing the AEL condition (AEL applied on the first repetition only) to the traditional (TRAD) loading condition. Correlated and hierarchical effects models, with robust variance estimation and small-sample adjustment, were fitted. Moderator analyses were used to examine whether ECC load (i.e., ECC load = vs. &gt; 100% TRAD one-repetition maximum [1RM]), loading differential (≥ vs. &lt; 40% TRAD 1RM), and exercise selection (back squat vs. bench press) influenced the acute effects of AEL across repetitions. Certainty of evidence was evaluated using the GRADE approach.</p> Results <p>The final analysis included 8 studies (106 participants, male: <i>n</i> = 90, female: <i>n</i> = 16). AEL significantly impaired mean barbell velocity during the subsequent CON phase immediately after its removal (effect size [ES] = -0.25, 95% confidence intervals [CI]: [-0.33, -0.16], <i>p</i> &lt; 0.001). The mean CON velocity impairment diminished by the second (ES = 0.01, 95% CI: [-0.10, 0.12], <i>p</i> = 0.822) and third (ES = 0.08, 95% CI: [-0.08, 0.23], <i>p</i> = 0.313) repetitions of the set. However, the certainty of evidence ranged from moderate to very low. Of all moderators examined, the application of AEL with the back squat resulted in greater velocity reductions during the first repetition only than those seen for the bench press (ES = -0.33 [back squat]; ES = -0.11 [bench press], <i>p</i> = 0.022).</p> Conclusion <p>AEL impaired the mean barbell velocity during the CON phase immediately after its removal compared with TRAD loading. This reduction in mean CON velocity appears greater in the back squat than in the bench press and is likely to dissipate across the subsequent repetitions following the removal of AEL.</p> <p><i>Protocol Registration</i> The original protocol was prospectively registered (<a href="https://doi.org/10.17605/OSF.IO/AYUJH">https://doi.org/10.17605/OSF.IO/AYUJH</a>) with the Open Science Framework.</p>