Data regarding the optimal dual antiplatelet therapy (DAPT) duration in patients treated with a 1- versus a 2-stent strategy in LM bifurcation PCI are scant. A literature search based on Cochrane Library, Embase, PubMed and Google Scholar was performed to locate articles published between January 2015 and January 2020. The following MeSH terms were used for the search: “Left Main” AND “DAPT Duration” AND “stent” OR “stenting”. The analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Occurrence of major adverse cardiovascular events (MACEs) according to length of DAPT and stenting strategy was analysed. A total of 256 articles were retrieved and after evaluation, 3 articles evaluating the results of 8 large registries were included into the analysis including a final population of 4117 patients [mean age 65.7 years, 3133 (76.0%) males]. A short-term DAPT resulted in a lower risk of MACEs in patients treated with a single stent strategy (OR: 0.49, 95% CI [0.33–0.67], p < 0.001, I2 = 0%), whereas a DAPT >12 months resulted in a significant higher risk of MACEs in the same group (OR: 7.39, 95% CI [5.09–10.7], p < 0.001, I2 = 61%) compared to double stent strategy. The available data support the use of short DAPT in single cross-over LM stenting whereas a long DAPT seems to be more appropriate after a double stenting strategy in LM bifurcation PCI.