Pharmacobezoars are an uncommon but potentially problematic manifestation of drug overdose. Diagnosed radiographically, endoscopically, intraoperatively, or postmortem, a bezoar is a mass of any form of unabsorbed material within the gastrointestinal tract. When they occur, they tend to form at anatomic strictures at any point between the esophagus and the rectum. They commonly occur in patients with prior abdominal surgery or altered GI motility. Besides obstructive and ischemic complications when impacted, pharmacobezoars can also cause prolonged toxicologic effects due to the retained drug mass. Venlafaxine is a bicyclic phenylethylamine antidepressant that inhibits serotonin, norepinephrine, and dopamine reuptake in the CNS. Morbidity and mortality from venlafaxine overdose are typically from seizures and cardiovascular toxicity. We describe a novel case of massive overdose of extended-release (ER) venlafaxine leading to obstructive pharmacobezoar formation at the ileocecal junction, with consequent bowel ischemia and necrosis requiring emergent hemicolectomy.