This is a case of a 44-year-old female with a history of irritable bowel syndrome, hypertension, hyperlipidemia, sleep apnea, gastric bypass surgery, and MTHFR polymorphism who presented to a walk-in clinic with five days of severe abdominal pain associated with diarrhea, nausea, and anorexia. Hypertension and tenderness over the right lower quadrant prompted a referral to the emergency department for evaluation of possible appendicitis. A contrasted computerized tomography (CT) scan of the abdomen and pelvis revealed a normal appendix and acute portal vein thrombosis. Here, MTHFR is linked to appendicitis.