Objective To investigate the clinical effect of esketamine on erector spinae plane block (ESPB) in elderly patients undergoing thoracoscopic surgery. Methods A total of 152 elderly patients, aged over 65 years, body mass index (BMI) 18.5‒30.0 kg/m2, American Society of Anesthesiologists (ASA) Ⅰ or Ⅱ, who were scheduled for thoracoscopic surgery in Xuzhou Cancer Hospital were selected. According to the random number table method, they were divided into two groups (n=76): an esketamine combined with ropivacaine for ESPB group (group A) and a ropivacaine for ESPB group (group L). Patients in both groups underwent ultrasound‑guided ESPB before anesthesia induction. Patients in group A were injected with 0.375% ropivacaine 150 mg+esketamine 0.5 mg/kg+normal saline in 40 ml, while those in group L were injected with 0.375% ropivacaine 150 mg+normal saline in 40 ml. The Mini‑Mental State Examination (MMSE) scores were used to assess patients' basic cognitive condition. MMSE scores were recorded 1 d before surgery, and at postoperative 1, 2, 3 d and 7 d. The intraoperative dosage of propofol and remifentanil, operation time and recovery time (from the end of operation to the time of tracheal catheter removal) were recorded. The effective times of patient‑controlled intravenous analgesia (PCIA) compression at postoperative 0‒6 h, 6‒12 h, 12‒24 h and 24‒48 h, Visual Analogue Scale (VAS) scores at rest and on coughing at postoperative 6, 12, 24 h and 48 h, and the incidence of postoperative delirium (POD) within postoperative 3 d and 7 d were recorded. Results Compared with group L, group A showed significantly decreased consumption of propofol and remifentanil (P<0.05), reduced effective times of PCIA compression at postoperative 0‒6 h, 6‒12 h and 12‒24 h (P<0.05), decreased VAS scores on coughing at postoperative 6, 12 h and 24 h (P<0.05), increased MMSE scores at postoperative 1 d (P<0.05), and reduced incidence of POD within postoperative 3 d (P>0.05). There was no difference in other indicators between the two groups (P>0.05). Conclusions Application of esketamine in ESPB can reduce the incidence of delirium within 3 d after surgery, significantly reduce the consumption of propofol and remifentanil in elderly patients with thoracoscopic surgery, with good postoperative analgesic effect.