Objective: To demonstrate that two lung ventilation under general anaesthesia may also be safely performed to create pericardial window with uniportal video-assisted thoracoscopic surgery.Method: The single-centre, retrospective, comparative study was conducted at Bulent Ecevit University, Zonguldak, Turkey, comprised data from March 2011 to March 2018 of patients with recurrent and/or with chronic large pericardial effusions unresponsive to medical therapy and/or to pericardiocentesis and who underwent pericardial window creation with uniportal video-assisted thoracoscopic surgery. Group 1 had data of patients in whom pericardial windows were created under general anaesthesia, while group 2 had patients with two lung ventilation. Parameters compared between the groups were gender, age, operation side, operation time amount of drainage, complication, recurrences and survival. Data was analysed using SPSS 19.Results: Of the 20 patients, 9(45%) were males and 11(55%) were females. Group 1 had 14(70%) patients, while group 2 had 6(30%). The age of patients in group 2 was significantly higher than those in group 1 (p=0.041). There was no significant difference between the groups with respect to gender, amount of drainage, operation time and post-operative complications (p>0.05). There was no recurrence or mortality in either of the two groups.Conclusions: Pericardial window could be created safely with video-assisted thoracoscopic surgery under two lung ventilation for patients carrying high risk for one lung ventilation.