Objectives: To assess the effects of thoracic paravertebral block and s-ketamine on postoperative pain and peri-operative neurocognitive disorder (PND) in video-assisted thoracoscopic surgery.Methods: Patients (n = 120) aged 45-65 undergoing video-assisted thoracoscopic surgery were allocated randomly into the following three groups: patients in the C group received general anaesthesia; patients in the thoracic paravertebral block group, i.e. the TP group, received general anaesthesia and ultrasound-guided par-avertebral block; and patients in the s-ketamine combined with ultrasound-guided thoracic paravertebral nerve block group, i.e. the TS group, received combined anaesthesia, which was administered as follows: general anaesthesia + ultrasound-guided paravertebral block + perioperative s-ketamine (a bolus of 0.3 mg/kg, followed by an infusion of 0.2 mg/kg/h until 30 min before the end of the surgical procedure).Results: Cognitive function was measured using the Mini-Mental State Examination 1 day preoperatively, 1 day postoperatively, and 3 months postoperatively. Z-score was used to determine the incidence of PND. Post-operative pain was assessed using the visual analogue scale at 0.5 and 24 h postoperatively. The use of opioid drugs, intraoperative vital signs, and other secondary outcomes were also recorded. The final analysis included a total of 110 patients. The intraoperative heart rate and mean arterial pressure in the TS and TP groups were lower than that for group C (P<0.05). After surgery, patients in the TS group exhibited significantly lower pain scores at 0.5 h and 24 h (P<0.001 and P = 0.004,respectively) as well as significantly lower rates of postoperative nausea, vomiting, and pulmonary complications (P<0.05). The incidence of PND in the TP and TS groups was lower than those who received general anaesthesia. However, there was no significant difference in the incidence of PND between the TP and TS groups (P>0.05).Conclusions: Ultrasound-guided paravertebral nerve block combined with s-ketamine decreased acute post-operative pain and improved the quality of recovery. However, perioperative s-ketamine did not improve cognitive function in patients under general anaesthesia with thoracic paravertebral block.