Objectives To describe the incidence of pleural effusion in patients who failed a first spontaneous breathing trial (SBT) and to describe the characteristics of these patients. Methods We conducted a prospective observational study in three medical ICU. All mechanically ventilated patients were screened daily. In patients who failed their first SBT, a pleural ultrasonography was performed and the presence of PE was qualitatively quantified according to a 4-steps classification: 0: no PE; 1: small PE; 2: moderate PE and 3: large PE. In addition the main clinical characteristics of patients were collected. For statistical analysis, patients with classes 0 and 1 were regrouped, as were patients with classes 2 and 3. Results From November 2014 to March 2015, 336 patients were screened and 56 (17%) failed their first SBT. Among them, 28 patients (50%) had no PE, 18 patients (32%) had small PE (left or right), 8 (14%) patients had moderate PE and 2 (4%) patients had large PE. Patients with moderate and large PE stayed longer in ICU (19 ± 7 vs. 9 ± 7 days, p < 0.01) and had a longer duration of mechanical ventilation (14 ± 9 vs. 24 ± 12 days, p < 0.01) as compared with patients without PE and with small PE. Patients with moderate or large PE and patients without PE or with small PE shared similar characteristics at admission (age: 66 ± 14 and 61 ± 15 and SAPS 2: 55 ± 18 53 ± 15, p > 0.05). Shock as the cause of initiation of mechanical ventilation was more frequent in patients with moderate and large PE as compared to patients without and small PE (40% vs. 4%, p < 0.01). Only one patient with a large PE had a pleural evacuation but without clinical improvement. Conclusions Significant pleural effusion is often detected in difficult to wean patients (18%), and is associated with shock state as the reason for mechanical ventilation. The interest of pleural drainage in this population deserves further studies.