Background: Hypothyroidism may affect immunological, wound-healing, and cardiovascular processes, which might worsen perioperative problems following large abdominal surgery. Although it is believed to reduce these hazards, the impact of thyroid hormone replacement therapy (THRT) in this situation is yet unknown. E objective was to evaluate the role of THRT in reducing perioperative complications among patients undergoing major abdominal surgeries. Methodology: This prospective cohort study was conducted at DHQ Teaching Hospital, KDA, Kohat, Pakistan from January to December 2023, involving 420 adult patients diagnosed with hypothyroidism. Participants were divided into two groups: those receiving THRT before surgery (THRT group) and those not receiving THRT (non-THRT group). Data on perioperative complications cardiovascular events, infections, delayed wound healing, and hospital stay were collected. Statistical analysis included chi-square tests, independent t-tests, and logistic regression. Results: The THRT group had fewer perioperative problems, such as delayed wound healing (3.81% vs. 7.14%), infections (7.62% vs. 10.00%), and cardiovascular events (5.71% vs. 7.62%), according to the research; nevertheless, these differences were not statistically significant (p > 0.05). In the THRT group, the average duration of hospital stay was lower (10.53 ± 2.19 days vs. 11.28 ± 2.32 days). In the THRT group, the total incidence of any perioperative complication was 11.43%, whereas in the non-THRT group, it was 15.24%. Conclusion: THRT may reduce perioperative complications in hypothyroid patients undergoing major abdominal surgeries, though the differences were not statistically significant.