Background: Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) and a wide QRS complex. However, up to 30–50% of patients fail to respond. The QRS Index, which quantifies QRS shortening after CRT, has emerged as a potential predictor of response. We aimed to perform a systematic review and meta-analysis to evaluate the association between QRS Index and CRT response. Methods: We searched PubMed, Scopus and Cochrane for studies reporting QRS Index values in CRT responders and non-responders. Studies defining response based on clinical, echocardiographic, or combined criteria were included. Heterogeneity was assessed using the I² statistic, and a random-effects model was applied. A meta-regression analysis explored the relationship between baseline echocardiographic parameters and QRS Index. Results: Nine studies with 1274 patients met the inclusion criteria, with 760 (59%) classified as responders and 514 (41%) as non-responders. The weighted mean ± standard deviation was 16.14 ± 13.19 in responders and 7.22 ± 14.96 in non-responders. The QRS Index was significantly higher in the responder group compared to non-responders (mean difference: 8.76; 95% CI: 6.45–11.06; I² = 45%; p < 0.00001). Meta-regression revealed that lower left ventricular end-systolic volume (LVESV) values were associated with even higher QRS Index in responders compared to non-responders (β = −0.0483; 95% CI: −0.0938; −0.0029, p = 0.0372). Conclusions: QRS Index is significantly higher in CRT responders, supporting its role as a predictor of response. Further studies are needed to standardize its clinical use and assess its prognostic impact.