<p>Left ventricular assist device (LVAD) implantation is a treatment option for advanced heart failure. The relationship between smoking and perioperative outcomes in LVAD implantation remains inconclusive, as evidence has been limited to single-center studies. This study aimed to examine the association between smoking and in-hospital outcomes of LVAD implantation in a large-scale population-based analysis. Patients who underwent LVAD implantation were selected from National Inpatient Sample from Q4 2015–2021. Multivariable logistic regression was used to compare in-hospital outcomes between smokers and non-smokers, where demographics, socioeconomic status, primary payer status, hospital characteristics, comorbidities, and transfer/admission status were adjusted. There were 1346 (26.5%) smokers and 3737 (73.5%) non-smokers who underwent LVAD implantation. Smokers presented with a higher burden of comorbidities. After multivariable adjustment, smokers had lower in-hospital mortality (aOR 0.68, 95 CI 0.52–0.889, p &lt; 0.01), MACE (aOR 0.74, 95 CI 0.554–0.987, p = 0.04), neurological complications (aOR 0.555, 95 CI 0.367–0.839, p = 0.01), stroke (aOR 0.508, 95 CI 0.311–0.832, p = 0.01), pericardial complications (aOR 0.705, 95 CI 0.545–0.913, p = 0.01), renal complications (aOR 0.691, 95 CI 0.595–0.801, p &lt; 0.01), venous thromboembolism (aOR 0.523, 95 C = 0.295–0.929, p = 0.03), hemorrhage/hematoma (aOR 0.746, 95 CI 0.641–0.869, p &lt; 0.01), and superficial wound complication (aOR 0.458, 95 CI 0.286–0.733, p &lt; 0.01). Moreover, smokers had a shorter time from admission to operation (p = 0.02), shorter length of stay (p &lt; 0.01), lower transfer out rate (p &lt; 0.01), and lower hospital charge (p &lt; 0.01). This study uncovered a “smoker’s paradox” in LVAD implantation. These findings added to the long-standing observation of a “smoker’s paradox” in cardiac surgery. However, the underlying reasons require further investigation. </p>