Patients with atrial fibrillation (AF), lasting >48 h, considered for cardioversion, are recommended ≥3 weeks of oral anticoagulation before sinus rhythm restoration because of high risk of development of left atrial thrombosis (LAT) and stroke. However, the optimal duration of anticoagulation in the presence of overt LAT is unknown. An open-label study aimed to investigate the prevalence of spontaneous echo contrast (SEC) and LAT before and after 3 weeks of direct oral anticoagulant (DOAC) treatment. We included 51 consecutive patients (50.9% males), mean age 69.3 ± 7.4 years with paroxysmal/unknown duration of AF, considered for cardioversion, who agreed to have transesophageal echocardiography at enrollment and 3 weeks later. At baseline SEC was present in 26 (50.9%) and LAT in 10 (19.6%) of 51 patients. After 3 weeks on DOAC, SEC persisted in 12 (25.0%) and LAT in 7 (14.5%) of 48 patients, < 0.05 vs. baseline. Factors, associated most strongly with persistence of SEC/LAT, were left atrial appendage (LAA) emptying velocity <20 cm/s (OR = 2.82), LAA lobes >2 (OR = 1.84), and indexed left atrial volume ≥34 mL/m (OR = 1.37). In our study the incidence of SEC/LAT, particularly in AF with unknown duration, was not as low as we expected. The prevalence of SEC/LAT seemed to be dependent on factors not routinely evaluated in AF patients planned for cardioversion (indexed LA volume, LAA morphology and number of lobules, LAA emptying velocity, etc.). Our data suggested an individualized approach for DOAC duration in AF patients before an attempt for restoration of sinus rhythm is made, taking into consideration the LAA morphology and function.