INTRODUCTION. Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure. Despite being less invasive than thoracotomy, post-operative pain remains a significant clinical problem. The aim of this study was to investigate if perioperative intravenous (IV) dexamethasone improves pain management in VATS. METHODS. Thirty-seven patients undergoing VATS with confirmed or suspected lung cancer were enrolled. The first 20 patients received standard care (Group 1) and the following 17 patients received standard care with addition of IV dexamethasone 8 mg (Group 2). The primary outcome was total opioid consumption during the first 24 hours after surgery. RESULTS. The baseline characteristics between groups were comparable. After adjusting for gender and duration of surgery, the median difference of total equianalgesic dose of opioid was 23 mg (p = 0.005). Group 2 had a significantly lower median pain score at rest. The first opioid dose was administered earlier in Group 1: 1.5 hours compared with to 6.9 hours in Group 2 (p = 0.020). Time to full mobilisation was longer in Group 1, with a mean of 12 hours (p = 0.018). CONCLUSION. This study suggests that addition of IV dexamethasone in VATS may reduce the need for opioids and facilitate early mobilisation. FUNDING. The study was funded by the Department of Clinical Medicine, Aalborg University, Aalborg, Denmark TRIAL REGISTRATION. The study is registered with ClinicalTrials.gov (NCT04633850). The study was conducted in accordance with the Declaration of Helsinki and all participants provided written consent.