Even with its broad spectrum and low cost, concern over chloramphenicol's adverse effects limited its use in the United States during the 1980s. Reports from United Kingdom and China in the 1990s demonstrated a low incidence of blood dyscrasias with the topical preparation of chloramphenicol, and showed continued good efficacy and low cost. Today, topical chloramphenicol is being used by some groups within otolaryngology and ophthalmology in the United States. As a result, emergency physicians are once again considering chloramphenicol-induced side effects in patients presenting to the emergency department. To date, there have been no published reports associating chest pain, dyspnea with chloramphenicol use, and there has only been one report of fungal esophagitis associated with topical chloramphenicol. We present a 31-year-old woman, 4 months status post tympanoplasty with a modified radical canal wall down mastoidectomy due to a cholesteatoma involving the epitympanum who had a residual tympanic membrane defect. She presented to the emergency department with chest "burning", with no other symptoms shortly after starting treatment with an insufflated combination antibiotic containing chloramphenicol. After ruling out cardiopulmonary or vascular etiology, she was treated successfully with a gastrointestinal cocktail cocktail for presumed esophagitis secondary to newly prescribed chloramphenicol.