In-stent restenosis (ISR) within bifurcation lesions of the left main (LM) coronary artery (LMCA) is challenging due to its complex anatomy and critical function. This case series highlights 3 patients with LM bifurcation ISR (Medina 1,1,1) post-index intervention using different stent strategies as follows: Case 1: A 58-year-old male developed distal LM bifurcation stenosis after ostial left anterior descending artery (LAD) stenting. Mini-culotte bifurcation angioplasty effectively managed this. Case 2: A 62-year-old male presented with neo-atherosclerosis-induced distal LM bifurcation ISR post-provisional LM-left anterior descending artery (LAD) stenting. A single-stent crossover with a drug-coated balloon in a large side branch achieved optimal flow restoration. Case 3: A chronic total occlusion in the right coronary artery and distal LM bifurcation ISR due to stent overhang into LMCA in a 72-year-old male was resolved with a string culotte technique. These cases underscore ISR management strategies tailored to patient-specific anatomy and clinical needs, advocating advanced imaging techniques like intravascular ultrasound and optical coherence tomography for procedural precision and safety.