Background: Digital nerve block (DB) is a commonly utilized anesthetic procedure in ingrown toenail surgery. However, severe procedure-related pain has been reported. Although the popliteal sciatic nerve block (PB) is widely accepted in foot and ankle surgery, its use in ingrown toenail surgery has not been reported. Therefore, this study aimed to investigate the safety and effectiveness of PB in the surgical treatment of ingrown toenails. Methods: One-hundred-ten patients surgically treated for an ingrown toenail were enrolled. Sixty-six patients underwent DB, and 44 underwent PB. PB was performed under ultrasound-guidance via a 22-gauge needle with 15 mL of 1% lidocaine in the popliteal region. The visual analogue scale was used to assess pain at two-time points: pain with skin penetration and pain with the solution injection. Time to sensory block, duration of sensory block, need for additional injections, and adverse events were recorded. Results: PB group demonstrated significantly lower procedure-related pain than the DB group. Time to sensory block was significantly longer in the PB group (20.8 ± 4.6 versus 6.5 ± 1.6 minutes). The sensory block duration was significantly longer in the PB group (187.9 ± 22.0 versus 106.5 ± 19.1 minutes). Additional injections were required in 16 (24.2%) DB cases, while no additional injections were required in PB cases. Four adverse events occurred in the DB group and two in the PB group. Conclusion: PB was a less painful anesthetic procedure associated with a longer sensory block duration and fewer repeat injections compared with DB. The result of this study implicates that PB can be an alternative anesthetic option in the surgical treatment of ingrown toenails.