Background: This systematic review and meta-analysis with trial sequential analysis (TSA) aimed to compare perioperative outcomes of peripheral nerve blocks (PNBs) and spinal anesthesia (SA) in elective foot and ankle surgery. Methods: The study protocol was registered in PROSPERO (CRD42021229597). Researchers independently searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs). Results: Analysis of nine RCTs (n = 802; 399 PNBs, 403 SA) revealed significantly shorter block performance times (WMD: 7.470; 95% CI 6.072 to 8.868), the onset of sensory (WMD: 7.483; 95% CI 2.837 to 12.130) and motor blocks (WMD: 9.071; 95% CI 4.049 to 14.094), durations of sensory (WMD: 458.53; 95% CI 328.296 to 588.765) and motor blocks (WMD: 247.416; 95% CI 95.625 to 399.208), and significantly higher postoperative analgesic requirements (SMD: −1.091; 95% CI −1.634 to −0.549) in the SA group. Additionally, systolic blood pressure (SBP) at 30 min (WMD: 13.950; 95% CI 4.603 to 23.298) was lower in the SA group. Conclusion(s): The SA demonstrated shorter block performance time, faster onset and shorter duration of sensory and motor blocks, higher postoperative analgesic requirements, and lower SBP at 30 min compared to PNBs in elective foot and ankle surgery.