Background and objectives: Quadripolar left ventricular (LV) leads in cardiac resynchronization therapy (CRT) offer multi-vector pacing with different pacing configurations and hence enabling LV pacing at most suitable site with better lead stability. We aim to compare the outcomes between quadripolar and bipolar LV lead in patients receiving CRT. Methods: In this prospective, non-randomized, single-center observational study, we enrolled 93 patients receiving CRT with bipolar (BiP) (n = 31) and quadripolar (Quad) (n = 62) LV lead between August 2016 to August 2019. Patients were followed for six months, and outcomes were compared with respect to CRT response (defined as ≥5% absolute increase in left ventricle ejection fraction), electrocardiographic, echocardiographic parameters, NYHA functional class improvement, and incidence of LV lead-related complication. Results: At the end of six months follow up, CRT with quadripolar lead was associated with better response rate as compared to bipolar pacing (85.48% vs 64.51%; p = 0.03), lesser heart failure (HF) hospitalization events (1.5 vs 2; p = 0.04) and better improvement in HF symptoms (patients with ≥1 NYHA improvement 87.09% vs 67.74%; p = 0.04). There were fewer deaths per 100 patient-year (6.45 vs 9.37; p = 0.04) and more narrowing of QRS duration (Δ12.56 ± 3.11 ms vs Δ7.29 ± 1.87 ms; p = 0.04) with quadripolar lead use. Lead related complications were significantly more with the use of bipolar lead (74.19% vs 41.94%; p = 0.02). Conclusions: Our prospective, non-randomized, single-center observational study reveals that patients receiving CRT with quadripolar leads have a better response to therapy, lesser heart failure hospitalizations, lower all-cause mortality, and fewer lead-related complications, proving its superiority over the bipolar lead.