Background: Left Main Coronary Artery (LMCA) disease is a high-risk subset of coronary artery disease, with bifurcation lesions comprising nearly 50% of cases. Advances in percutaneous coronary intervention (PCI) using drug-eluting stents (DES) and drug-coated balloons (DCB) offer novel treatment options. This study compares the efficacy and safety of DES with DCB versus the conventional two-stent technique in treating left main bifurcation lesions. Methods: This observational study included 60 patients with true left main bifurcation lesions undergoing revascularization at Benha University. Patients were divided into two groups: Group I (DES + DCB) and Group II (2-DES). Pre- and post-procedure intravascular ultrasound (IVUS) assessments were performed. All participants received dual antiplatelet therapy and statins. Follow-up was conducted over six months through medical records, outpatient visits, and telephone consultations. Results: In the LAD artery, the 2-DES group demonstrated lower postoperative luminal stenosis (8.4 ± 1.8%) compared to DES + DCB (10.19 ± 1.58%, P = 0.003). In the left circumflex artery, the 2-DES group had a higher minimum luminal diameter (3.3 ± 0.27 mm vs. 3 ± 0.37 mm, P = 0.01) and lower luminal stenosis (12.02 ± 2.42% vs. 20.31 ± 3.85%, P < 0.001). Major adverse cardiac events (MACE) occurred in 10% of the 2-DES group and 3.3% of the DES + DCB group (P = 0.612). Conclusion: The two-stent technique achieved superior immediate postoperative luminal outcomes, while DES + DCB demonstrated comparable safety and efficacy with a lower incidence of MACE at six months.