Background <p>Poor left ventricular ejection fraction (LVEF) is associated with an increased risk of left ventricular (LV) thrombus formation. However, the effect of LVEF on thrombus resolution remains unclear.</p> Methods <p>We prospectively enrolled patients from 2020 to 2022 and retrospectively from 2010 to 2020 at the National Center for Cardiovascular Diseases, China. Patients with LV thrombus diagnosed within the last 3 months were included. The primary outcome was the resolution of LV thrombus at 12 weeks. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression, adjusting for potential covariates.</p> Results <p>A total of 380 patients on oral anticoagulation for ≥ 12 weeks were included, with a median age of 50.8 years (81.6% male). Dilated cardiomyopathy was the most common underlying condition (51.6%). Direct oral anticoagulants (DOACs) were prescribed to 53.7% of patients. The median baseline LVEF was 30%. In unadjusted analysis, thrombus resolution was higher in patients with LVEF ≤ 30% (78.5% vs. 63.9%, HR 0.61, 95%CI 0.48–0.78, <i>P</i> &lt; 0.001). However, after adjustment for confounders, the difference was not significant (HR 0.79, 95%CI 0.61–1.03, <i>P</i> = 0.089). In multivariable analysis, DOAC use was associated with a higher likelihood of thrombus resolution compared to warfarin (HR 1.34, 95% CI 1.04–1.74, <i>P</i> = 0.024).</p> Conclusions <p>Baseline LVEF was not a significant predictor of LV thrombus resolution after adjustment. DOACs were more effective than warfarin in promoting thrombus resolution, warranting further investigation.</p> Trial registration <p>This study was a combined cohort from two studies (ClinicalTrials.gov: NCT04970381, NCT 05006677).</p>