Thoracic surgeries are associated with intense postoperative pain. General opioid analgesia is still the main anaesthetic method. Due to the large number of opioid-induced side effects, alternative methods of pain relief are sought. One of them is the use of balanced analgesia, which consists of regional analgesia, non-opioid painkillers, and small doses of opioids. The objective of this study was to assess the effectiveness of preoperative thoracic paravertebral block (ThPVB) in the treatment of postoperative pain after video-assisted thoracic surgery (VATS) by measuring hormone levels in blood serum or saliva. It was a randomised, open-label study conducted in a single university hospital setting between May 2018 and September 2019. In total, 119 patients were scheduled for elective video-assisted thoracic surgery. Performed interventions included: preoperative thoracic paravertebral block with 0.5% bupivacaine, followed by postoperative oxycodone combined with nonopioid analgesics. Follow-up period comprised first 24 hours and one, two, and six months after surgery. Main outcomes were measured by pain intensity assessed using the Numerical Rating Scale (NRS) and the levels of the following hormones: testosterone, cortisol, α-amylase activity, sIgA, and β-endorphin. A total of 119 patients were randomised into two groups and, of these, 49 were subsequently excluded from the analysis. The final analysis included 37 patients from the study group and 33 from the control group. There were no statistically significant differences in the analysed parameters the relative change T1-T0. There was a tendency towards statistical significance in the relative change T2-T0 in testosterone levels. At rest, no statistically significant differences were found between groups and time in the percentage of patients with NRS ≥ 1. During cough, the percentage of patients with NRS ≥ 1 was higher at T1 and T2 time points in the ThPVB group. Of the factors considered, only α-amylase levels statistically significantly increased the chance for higher NRS score after a month [OR = 1.013; 95% PU: 1.001-1.025; p < 0.01]. ThPVB is effective and safe for patients undergoing VATS. It can be an effective alternative for general anaesthesia using high doses of opioids.