Objective To verify the safety and efficacy of a dry-sealed thoracic drainage device. Methods This study was a prospective, single-center, randomized, parallel controlled, non-blind and non-inferiority clinical trial. Block randomization was used. A total of 72 patients who received lobotomy and postoperative thoracic drainage in Shanghai Chest Hospital of Shanghai Jiao Tong University from Jan. 2017 to Jun. 2019 were selected and randomly assigned to experimental group and control group, with 36 patients in each group. The experimental group used a disposable dry-sealed thoracic drainage device, and the control group used a disposable thoracic drainage bottle for gas and/or fluid drainage in the pleural cavity. Full analysis set (FAS), per-protocol set (PPS) and safety set (SS) were set up to evaluate the effect of fluid drainage (recovery rate of pleural effusion), ventilation effect (good recovery rate of lung inflation) and safety in the 2 groups. Results Among the 72 cases, 3 patients were excluded because their hospitalization age exceeded the inclusion criteria, and the exclusion rate was 4.17% (3/72). FAS included all 72 subjects, 36 in the control group and 36 in the experimental group; 69 subjects in PPS, 36 in the control group and 33 in the experimental group; and 72 subjects in the SS, 36 in the control group and 36 in the experimental group. The results of FAS analysis showed that the good recovery rate of pleural effusion was 100.00% (36/36) in the control group, and that in the experimental group was 100.00% (36/36); the non-inferiority margin was 7.00%, the difference between the 2 groups was 0.00% (95% confidence interval[CI] 0.00%-0.00%), and its lower limit absolute value was lower than the non-inferiority margin. The good recovery rate of lung inflation was 69.44% (25/36) in the control group and 77.22% (26/36) in the experimental group, and the difference between the 2 groups was 2.78% (95% CI -18.21%-23.77%), showing no significant difference (P>0.05). The results of PPS analysis showed that the good recovery rate of pleural effusion was 100.00% (36/36) in the control group, and that in the experimental group was 100.00% (33/33), with the difference between the 2 groups being 0.00% (95% CI 0.00%-0.00%) and the lower limit absolute value being lower than the non-inferiority margin; the good recovery rate of lung inflation was 69.44% (25/36) in the control group and 69.70% (23/33) in the experimental group, and the difference between the 2 groups was 0.25% (95% CI -21.48%-21.98%), showing no significant difference (P>0.05). SS analysis results showed that the dry-sealed thoracic drainage device and the closed thoracic drainage bottle both had good sealing performance during the whole experiment, the connecting port did not fall off, and there were no clinical adverse events. Conclusion The application of dry-sealed thoracic drainage device in postoperative patients plays positive roles in fluid and/or gas drainage with good safety. It is a good supplement to the drainage method of water-sealed thoracic bottle and worthy popularizing.