Background/Objective: Wound infiltration with local anesthetics emerges as a promising modality for postoperative pain alleviation. However, such strategies in neck surgery have not been a well-established practice. To assess wound infiltration with ropivacaine plus magnesium sulfate for pain relief following thyroid surgery. Methods: This prospective, double-blind, randomized study enrolled 68 patients who underwent thyroid surgery. Concerning the solution used for surgical wound infiltration, the study participants were randomly allocated into three groups: (1) 100 mg of ropivacaine (Group R); (2) 100 mg of ropivacaine plus magnesium sulfate 10 mg/kg (Group RMg); and (3) normal saline which served as a placebo (Group P). Pain perception both at rest and at movement, was measured using the Visual Analogue Scale (VAS) at 30 min, as well as at 1, 2, 4, 6, 12, and 24 h postoperatively. The total consumption of analgesics in morphine equivalents was also recorded. Moreover, adverse effects and patient satisfaction were recorded. Cortisol, TNF-α, and IL-6 levels were measured 30 min before infiltration and 6 h and 24 h postoperatively. Results: Demographics and clinical characteristics were similar between the groups. The VAS scores at rest and during movement were significantly lower in the RMg group compared to the saline or ropivacaine groups. Total analgesic consumption was also significantly lower in the RMg group. No operation-, wound-, or infiltration-related adverse effects were recorded in the study groups. Better overall satisfaction was obtained for the RMg group. Conclusions: Ropivacaine plus magnesium sulfate wound infiltration provided better pain control and the analgesic effect was more significant, contributing to effective postoperative analgesia in patients undergoing thyroid surgery.