Background <p>Post-induction hypotension (PIH) is a frequent complication during general anesthesia and is linked to adverse outcomes. Abnormalities in serum total cholesterol (TC) have been associated with blood pressure dysregulation. This study investigated the relationship between preoperative serum TC levels and the risk of PIH in elderly patients undergoing non-cardiac surgery.</p> Methods <p>We retrospectively reviewed 821 elderly patients who received general anesthesia for non-cardiac surgery at our hospital between January 2019 and December 2021. Patients were categorized into a high TC group (≥ 5.2 mmol/L) and a normal TC group (&lt; 5.2 mmol/L). Propensity score matching (PSM) was performed to reduce baseline differences, and perioperative hemodynamic outcomes were compared.</p> Results <p>PIH incidence was significantly higher in the high TC group than in the normal TC group (50.6% vs. 27.3%, <i>p</i> = 0.003). After PSM (<i>n</i> = 144 per group), the unadjusted risk of PIH was 1.74 times higher in the high TC group (95% confidence intervals [CI]: 1.24–2.45). Following adjustment for residual confounders, the increased risk persisted (adjusted risk ratio: 1.58; 95% CI: 1.12–2.23). Patients with high TC also showed greater reductions in blood pressure before (32% vs. 26%, <i>p</i> = 0.009) and after intubation (23% vs. 17%, <i>p</i> = 0.011).</p> Conclusions <p>Elevated preoperative serum TC is independently associated with a higher risk of PIH in elderly patients undergoing non-cardiac surgery. These results suggest that cholesterol metabolism contributes to perioperative hemodynamic instability and underscores the importance of including lipid status in preoperative risk assessment and anesthetic planning.</p>