Abstract Introduction Left main bifurcation (LMB) disease represents a high-risk subset of advanced coronary artery disease, often associated with severe calcification. Different stenting techniques have been evaluated to overcome challenges of the LMB anatomy, but the role of the calcific burden on cardiovascular (CV) outcome after LMB revascularization is unclear. Purpose We sought to evaluate the CV hospitalization predictors during follow-up of patients who underwent LMB revascularization (LMBR) in a high-volume center in Italy. Methods We performed a retrospective analysis of LMBR patients between 2018 and 2021. Patients were treated with different techniques in the acute or chronic settings and followed-up by telephone or outpatient visit. Coronary calcification (CC) was visually judged as absent, mild, moderate or severe. Predictors of CV hospitalizations were assessed. Results The median follow-up was 511 days. Among 129 patients who underwent LMBR during the study period, 32 (24.8%) were female, with a mean age of 72 (±10.6) years. 105 (81.4%) patients were hypertensive and 49 (38%) diabetics. The mean eGFR value was 66.3 (± 21.8) ml/min/m2. The majority of patients had three vessel disease (79, 61.3%), while only a small minority had one vessel disease (5, 3.9%). The mean SYNTAX score I was 27.1 (± 8.6), with most patients at intermediate risk (65, 50.4%) followed by patients at low (37, 28.7%) and high (27, 20.9%) risk. A provisional technique was used in most cases (79, 61.2%), followed by double-kissing crush (37, 28.7%) and T-stent/T-and-protrusion (13, 10.1%). Intravascular imaging was used in 84 (65.1%) cases. Most patients had no angiographic demonstration of CC (73, 57.9%), while when present, they were mild in 14 (11.1%), moderate in 29 (23%) and severe in 10 (7.9%) patients. Preparation of the CC was performed only with non-compliant (NC) balloons in mild CC (10, 71.4%) and with NC balloons (14, 48.3%) or intravascular lithotripsy (IVL) (13, 44.8%) in case of moderate CC. In the presence of severe CC, lesion preparation was carried out with IVL (4, 40%) or NC balloons (6, 60%). CC were associated with a more unfavorable outcome and, when present in a severe grade, resulted in a statistically significant risk of CV hospitalizations (HR 1.652; 95% CI 1.723–15.793; p=0.003) (Figure 1). After univariate and multivariate Cox regression analysis (Figure 2), only the presence of severe CC was associated with an increased risk of CV hospitalizations (HR 1.9; 95% CI 1.76–19.63; p=0.002), whereas aspirin therapy was a protective factor (HR −1.34; CI 0.07–0.86; p=0.02). Conclusions The presence of severe calcification is associated with a higher risk of CV hospitalizations, despite preparation of calcific lesions was always performed and intravascular imaging use was extensive. There were no differences in outcomes regardless to clinical presentation at admission, different stenting techniques and SYNTAX score I. Funding Acknowledgement Type of funding sources: None.