(1) Background: Orthopedic surgery has been transformed by 3D-printed personalized instruments (3DP-PSIs), which enhance precision and reduce complications. Hospitals are adopting in-house 3D printing facilities, using cost-effective methods like Fused Deposition Modeling (FDM) with materials like Polylactic acid (PLA) to create 3DP-PSI. PLA’s temperature limitations can be overcome by annealing High-Temperature PLA (ann-HTPLA), enabling steam sterilization without compromising properties. Our study examines the in vivo efficacy of ann-HTPLA 3DP-PSI in pediatric orthopedic surgery. (2) Methods: we investigated safety and efficacy using ann-HTPLA 3DP-PSI produced at an “in-office” 3D-printing Point-of-Care (3DP-PoC) aimed at correcting limb deformities in pediatric patients. Data on 3DP-PSI dimensions and printing parameters were collected, along with usability and complications. (3) Results: Eighty-three ann-HTPLA 3DP-PSIs were utilized in 33 patients (47 bone segments). The smallest guide used measured 3.8 cm3, and the largest measured 58.8 cm3. Seventy-nine PSIs (95.2%; 95% C.I.: 88.1–98.7%) demonstrated effective use without issues. Out of 47 procedures, 11 had complications, including 2 infections (4.3%; 95% CI: 0.5–14.5%). Intraoperative use of 3DP-PSIs did not significantly increase infection rates or other complications. (4) Conclusions: ann-HTPLA has proven satisfactory usability and safety as a suitable material for producing 3DP-PSI in an “in-office” 3DP-PoC.