Norethindrone acetate/ethinyl estradiol (Estrostep; Warner Chilcott, Rockaway, New Jersey) is an "estrophasic" type of oral contraceptive, which combines a continuous low progestin dose with a gradually increasing estrogen dose. In clinical trials, this medication failed to produce clinically significant changes in serum lipid levels. We report a case of severe hypertriglyceridemia-induced acute pancreatitis in a 24-year-old woman caused by Estrostep, occurring nearly 10 years after she began using the drug. The patient was admitted to the medical intensive care unit (ICU) for aggressive volume resuscitation and management of severe electrolyte abnormalities. Laboratory studies obtained on admission indicated severe hypertriglyceridemia (2,200 mg/dL), hyponatremia (120 mEq/L), and hypocalcemia (0.78 mmol/L). Amylase and lipase levels were also elevated (193 and 200 U/L, respectively). Ranson score calculated after 48 hours of admission was 4, and her Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 35. Treatment included an insulin infusion, ω-3 fatty acid esters, and gemfibrozil. The insulin infusion reduced serum triglyceride levels by 50% after 1 day of treatment and to 355 mg/dL by day 7 of her ICU course. We believe that this is the first reported case of severe, acute hypertriglyceridemia-induced pancreatitis caused by this medication.