With the expanding utilization of hyaluronic acid (HA) and collagen as cosmetic fillers in plastic and reconstructive surgery, complications due to their excessive use and/or irregular procedures warrant great caution. Recently, a fatal case occurred caused by a poorly regulated procedure of vaginal injection of HA and collagen. A 33-year-old female was admitted to the emergency department 3 hours after the operation with a chief complaint of dyspnea, which initiated 5 to 10 minutes after the operation. Her blood pressure remained low while dopamine pressor and fluid replacement were used. Computed tomography of the chest showed local exudation in the lower lobe of the left lung, enlargement of right atrium and ventricle, and uneven development of the bilateral inferior lobar artery with filling defects. Pulmonary computed tomography angiography and three-dimensional reconstruction showed continuous interruption of pulmonary artery branches of the posterior basal segment of the right lower lobe. Unfortunately, the clinical symptoms caused by vaginal injection aggravated rapidly and could not be effectively controlled. The patient died 9 hours after injection. Pulmonary complications after injection of cosmetic fillers are scarcely reported. Thus far, only 2 cases of HA-related pulmonary complications after vaginal injection have been described. The present case emphasizes that surgeons and other healthcare providers must be aware of the risk of serious pulmonary complications and even death associated with these 2 widely utilized injectable fillers. Level of Evidence: 5. © 2019 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.