PURPOSE To report 11 cases of adverse systemic reactions to topical ocular application of phenylephrine 10% in pledget form and to discourage this method of treatment for hemostasis in laser assisted in-situ keratomileusis (LASIK) surgery and other ophthalmic uses. DESIGN Observational case series. METHODS The literature, reports provided to the spontaneous reporting system of the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon) were reviewed. Age, sex, duration of therapy, other drugs the patient was taking, and systemic reactions are provided in the series of 11 cases with adverse systemic reactions. RESULTS Eleven cases of adverse systemic reactions to topical ocular phenylephrine 10% applied in pledget form occurred in 8 male and 3 female patients with an age range from 1 to 76 years. All cases occurred after a single exposure, most patients noted systemic effects within minutes of phenylephrine application, and the adverse systemic reactions included severe hypertension, pulmonary edema, cardiac arrhythmia, cardiac arrest, and subarachnoid hemorrhage. CONCLUSIONS We recommend ophthalmologists not use this method of phenylephrine application and believe it is contraindicated in ophthalmic surgery, especially when other medications may be used.