Background <p>With the acceleration of population aging in China, the incidence of postoperative neurocognitive dysfunction (PND) will continue to rise.</p> Aim <p>We aim to evaluate whether the precursor of brain-derived neurotrophic factor (proBDNF) and mature brain-derived neurotrophic factor (mBDNF) are associated with PND in elderly patients.</p> Methods <p>Eighty-six patients who were scheduled for elective orthopedic surgery under general anesthesia were ultimately enrolled. Referring to previous studies, the patients were divided into the PND group and the non-PND group with the Montreal Cognitive Assessment (MoCA) scale on postoperative day 7. The <i>Spearman</i> test was used to determine the correlations between mBDNF, proBDNF, and PND.</p> Results <p>All the participants possessed normal cognitive function before surgery. Compared with those in the nPND group, proBDNF, mBDNF, proBDNF*mBDNF, and MoCA score (all <i>P</i> &lt; 0.001) were lower in the PND group after surgery. The <i>Spearman</i> test showed PND was correlated with postoperative proBDNF (correlation coefficient = -0.391; <i>P</i> = 0.001), mBDNF (correlation coefficient = -0.295; <i>P</i> = 0.006), proBDNF*mBDNF (correlation coefficient = -0.479; <i>P</i> &lt; 0.001), and the ratios of proBDNF (correlation coefficient = -0.388; <i>P</i> &lt; 0.001) and mBDNF (correlation coefficient, -0.375; <i>P</i> &lt; 0.001) from before to after surgery.</p> Discussion <p>In this study, PND was significantly associated with postoperative proBDNF and mBDNF; the diagnostic value of postoperative mBDNF combined with proBDNF was superior to that of either index alone.</p> Conclusions <p>The PND was significantly associated with postoperative proBDNF and mBDNF.</p> Trial registration <p>Chinese Clinical Trial Registry (ChiCTR1800017415, registered date: 07/29/2018), <a href="http://www.chictr.org.cn">http://www.chictr.org.cn</a>.</p>