Background: Uniportal thoracoscopic surgery has become widely accepted for its favourable outcomes with regard to pain. However, post-operative pain is still a concern associated with thoracic surgery. The objective of this study was to evaluate the post-operative pain of patients undergoing uniportal video-assisted thoracoscopic surgery (VATS) lobectomies using an intra-operative intercostal nerve block. Methods: All consecutive patients undergoing uniportal VATS lobectomies between October 2018 and October 2019 were reviewed retrospectively. Twenty consecutive patients in Group A underwent uniportal VATS lobectomies without intra-operative intercostal nerve blocks. The other 20 consecutive patients in Group B underwent uniportal VATS lobectomies with intra-operative intercostal nerve blocks. Numeric Pain Rating Scale (NRS) scores were recorded at 1, 12 and 24 h postoperatively. The number of anti-inflammatory drugs (non-steroidal anti-inflammatory drug [NSAIDs]) consumed until the time of chest tube removal was also recorded. Results: There was no difference between the groups with regard to sex, age, chest tube duration, length of stay, operative time or laterality. There was a significant difference in post-operative NRS scores at 1 h ( P < 0.001) and 12 h ( P = 0.014) between the groups. The NSAID consumption was significantly lower in Group B than in Group A ( P = 0.038). Conclusion: Intra-operative intercostal nerve blocks with bupivacaine provided immediate post-operative pain relief and reduced post-operative opioid consumption in patients who underwent uniportal VATS lobectomies.