Background: Drainless minimally invasive video-assisted thoracoscopic surgery (VATS) has improved perioperative outcomes and has become the standard of care for many thoracic procedures. Objectives: This study aimed to assess safety and perioperative outcomes of omitting chest tube drainage after VATS among eligible selected patients Methods: This study included 48 patients eligible for VATS and fulfilling the inclusion and exclusion criteria of omitting chest tube drain where, they were randomly allocated into two groups: Group-I (Drainless group) included 24 patients undergoing VATS with intra operative omitting of chest tube drains after an air leakage test and group-II (Drainage group) that included 24 patients undergoing VATS with conventional treatment using standard chest tube drainage. Results: Omitting chest tube drainage improved the median of operation time (116.0 minutes), average post-operative pain score per day (1.66) and shortened median of postoperative duration of hospital stay (1.0 days) among patients in drainless group-I compared to 139 minutes, 4.8 and 3.5 days among patient in drainage group-II (P<0.001) respectively. Uniportal VATS procedure, VATS sympathectomy, male sex, younger age and non-smoking habits in eligible selected patients with omitting chest tube drainage among them expressed significantly the lowest postoperative pain score, shortest postoperative duration of hospital stay and the least operation time with minimal risk of perioperative complications compared to drainage group-II (P<0.01). Conclusions: Omitting chest tube drainage after VATS is feasible in eligible selected patients and improved its efficacy, safety and perioperative outcomes (postoperative pain, hospital stay length, and the risk of perioperative complications).