Objective: The validity of video-assisted thoracoscopic pericardial fenestration was prospectively assessed for loculated effusions, effusions previously treated by percutaneous catheter manoeuvres and those with concurrent pleural diseases. Methods: Inclusion criteria consisted of echocardiographically documented pericardial effusions requiring diagnosis or relief of symptoms and recurrent effusions after failed percutaneous drainage and balloon pericardiotomy. Pre-operative CT-scan was used to delineate additional pleural pathology and to determine the side of intervention. All patients were followed clinically and by echocardiographic examination 3 months post-operatively. Results: Twenty-four patients underwent thoracoscopic pericardial fenestration with 11 patients (54%) being previously treated by percutaneous catheter drainage, balloon pericardiotomy or subxyphoidal fenestration. Pre-operative echocardiography revealed septation and loculation in 18 patients (72%). Additional pleural pathology was identified on CT scan in 12 patients (50%) and talc pleurodesis was performed in six patients, all suffering from malignant pleural effusion. The mean operation time was 45 min (range 30-60 min) with no complications being observed. All patients were followed 3 months post-operatively by clinical and echocardiographic examination; relief of symptoms was achieved in all patients but echocardiography showed a recurrence in one patient (4%). Another recurrence was found by echocardiography after a mean follow-up time of 33 months in the 12 patients suffering from a non-malignant pericardial effusion. No recurrence of pleural or pericardial effusion was observed in the subset of patients with talc pleurodesis. Conclusion: Video-assisted thoracoscopic pericardial fenestration is safe and effective for loculated pericardial effusions previously treated by percutaneous drainage manoeuvres and those with concomitant pleural diseas