Objectives Evaluate safety and efficacy of polymer‐free biolimus‐eluting stents (PF‐BESs) versus ultrathin stents in unprotected left main (ULM) or bifurcation. Background PF‐BESs due to reduced length of dual antiplatelet therapy (DAPT) are increasingly used. However, there are limited data about safety and efficacy for ULM or bifurcation. Methods We selected all‐patients treated for ULM or bifurcation from two multicenter real life registries (RAIN NCT03544294 evaluating ultrathin stents, CHANCE NCT03622203 appraising PF‐BES). After propensity score with matching, the primary endpoint was major adverse cardiac events (MACE; a composite of all‐cause death, myocardial infarction, target lesion revascularization TLR, and stent thrombosis ST), while its components along with target vessel revascularization (TVR) secondary endpoints. Results Three thousand and three patients treated with ultrathin stents and 446 with PF‐BESs, resulting respectively in 562 and 281 after propensity score with matching (33 and 22%, respectively, with ULM disease). After 12 (8–20) months, rates of MACE were similar (9 vs. 8%, p = 0.56) without difference in TLR and ST (3.0 vs. 1.7%, p = .19 and 1.8 vs. 1.1%, p = .42). These results were consistent for ULM group (3 vs. 1.7% and 1.8 vs. 1.1%, p = .49 and .76), for non‐ULM group (2.1 vs. 3.4%, p = .56 and 1.2 vs. 1.7%, p = .78) and for two‐stent strategy (8.7 vs. 4.5% and 4.3 vs. 3.2%, p = .75 and .91). Among patients treated with 1 month of DAPT in both groups, those with ultrathin stents experienced higher rates of MACE related to all‐cause death (22 vs. 12%, p = .04) with higher although not significant rates of ST (3 vs. 0%, p = .45). Conclusions PF‐BES implanted on ULM or BiF offered freedom from TLR and ST comparable to ultrathin stents. PF‐BESs patients assuming DAPT for 1 month experienced a lower despite not significant incidence of ST.