Objective: To report a case of myxedema megacolon complicated with sigmoid volvulus that was successfully managed with surgery and intensive thyroid hormone replacement therapy (THRT). Methods: The clinical presentation, laboratory and imaging results, treatment of the myxedema megacolon episode, and post-surgical evolution with THRT are presented. Results: We present the case of a 17-year-old woman with history of congenital hypothyroidism, chronic constipation, and irregular treatment with levothyroxine, who was admitted to the emergency room following 7 days of abdominal pain, nausea, and vomiting. She presented with marked abdominal distention and without bowel sounds. An abdominal computerized tomography scan showed a severe colon enlargement. Thyroid-stimulating hormone (TSH) was 222 μIU/mL, total thyroxine was <1 μg/dL, and total triiodothyronine was <40 ng/dL. Exploratory laparotomy was performed. Sigmoid volvulus was found and sigmoidectomy was performed. No evidence of colonic obstruction was found, but her clinical condition did not improve. After 1 month of mixed replacement therapy with levothyroxine 150 μg/day plus liothyronine 25 μg/day, intestinal movements were re-established and she was discharged asymptomatic with a TSH level of 0.15 μIU/mL. Conclusion: Myxedema megacolon is a rare clinical manifestation of hypothyroidism that, when complicated by sigmoid volvulus, is diagnostically and clinically challenging. History of constipation, thyroid disease, signs and symptoms of hypothyroidism, poor treatment compliance, or lack of improvement after abdominal surgery should raise suspicion to identify these patients due to the high risk of anesthetic and post-surgery complications. In our case, a dual combination of levothyroxine plus liothyronine resulted in clinical and biochemical recovery. Abbreviations: CH = congenital hypothyroidism; GI = gastrointestinal; GIT = gastrointestinal tract; IV = intravenously; NR = normal range; THRT = hormone replacement therapy; TSH = thyroid-stimulating hormone