Muscle relaxants are commonly prescribed in the United States but may have deleterious side effects that are unrecognized by physicians. Here, we report a 55-year-old Caucasian man who developed pancreatitis and a subsequent hyperosmolar hyperglycemic state after being prescribed tizanidine. The patient had untreated hypertriglyceridemia, unbeknownst to the prescribing physician. While hypertriglyceridemia is a widely understood risk factor for pancreatitis, its incidence with tizanidine is not. As an alpha-2 agonist, tizanidine slows gastrointestinal motility by inhibiting gastrointestinal smooth muscle contraction, which could lead to ileus which occurred in this patient. Alpha-2 agonists further contract the hepato-pancreatic sphincter, which may result in obstruction of pancreatic enzyme flow via the pancreatic duct. This patient's case of pancreatitis was precipitated by 2 factors: (i) his use of tizanidine and (ii) hypertriglyceridemia. This case demonstrates that patients presenting with severe hypertriglyceridemia, or other potential risk factors for pancreatitis, should not be prescribed tizanidine.