Background <p>Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities detected during the perioperative periods and can significantly impede patient recovery. Thoracic surgery is a highly invasive procedure and is linked to an increased risk of PND. Although paravertebral block (PVB) is effective in providing postoperative analgesia following thoracic procedures, robust evidence linking PVB to lower PND risk remains limited.</p> Objective <p>This study aimed to evaluate the efficacy of programmed intermittent paravertebral analgesia (PIPA) on delayed neurocognitive recovery (dNCR) at postoperative 3&#xa0;days in elderly patients undergoing video-assisted thoracoscopic surgery (VATS).</p> Methods <p>This prospective, randomized controlled trial enrolled 228 elderly patients scheduled for elective VATS of the lungs. Patients were randomly assigned to one of two postoperative analgesia groups: the paravertebral block group (Group P), which received paravertebral infusion of 0.2% ropivacaine hydrochloride at 300&#xa0;mL, or the intravenous patient-controlled analgesia group (Group I), which received sufentanil (2&#xa0;μg/kg, diluted to 100&#xa0;mL).</p> Results <p>A total of 190 patients were included in the primary complete-case analysis. The incidence of delayed neurocognitive recovery (dNCR) at 72&#xa0;h postoperatively was significantly lower in the Group P compared to the Group I (33.3% vs. 55.3%, RR = 0.404 [0.224, 0.727], <i>p</i> = 0.002). The sensitivity analysis incorporating all 228 randomized patients with 72-h cognitive data confirmed this finding (Group P 32.5% vs. Group I 52.6%, <i>p</i> = 0.003), and the effect remained robust after adjustment for age and baseline MoCA score (adjusted OR = 0.43, 95% CI 0.25–0.76, <i>p</i> = 0.004). Furthermore, the incidence of dNCR at 30&#xa0;days (12.5% vs. 25.5%, <i>p</i> = 0.022) and postoperative neurocognitive disorder at 3&#xa0;months (5.2% vs. 19.1%, <i>p</i> = 0.003) postoperatively showed statistically significant differences between the Group P and the Group I. Regarding acute pain, both active (3 [2, 4] vs. 3 [2, 5], <i>p</i> = 0.037) and coughing (4 [3, 5] vs. 4 [4, 5], <i>p</i> = 0.015), Numeric Rating Scale (NRS) scores at 24&#xa0;h postoperatively were significantly lower in the Group P than Group I. At 3&#xa0;months postoperatively, resting NRS scores remained significantly lower in the Group P (1 [0, 2] vs. 2 [0, 2], <i>p</i> = 0.033). Additionally, the incidence of neuropathic pain (20.2% vs 34.0%,<i> p</i> = 0.03) and chronic postsurgical pain (3.2% vs. 11.7%,<i> p</i> = 0.025) at 3&#xa0;months was significantly reduced in the Group P compared to the Group I.</p> Conclusion <p>In elderly patients undergoing VATS, PIPA was associated with a lower incidence of MoCA-defined dNCR and postoperative neurocognitive disorder, as well as lower incidences of chronic postsurgical pain and neuropathic pain, compared with conventional opioid-based intravenous analgesia.</p> Trial registration <p>The study was registered in the Chinese Clinical Trial Registry on June 30, 2022 (ChiCTR2200061670).</p>