Oral pseudoephedrine is a common ingredient in more than 135 over-the-counter and prescription medications.1,2 Brands of common over-the-counter and prescription decongestants that contain pseudoephedrine include Allegra-D, Alka-Seltzer Plus Cold Medicine Liqui-Gels, Aleve Cold and Sinus Caplets, Benadryl Allergy and Sinus Tablets, Claritin-D Non-Drowsy 24 Hour Tablets, Contac Non-Drowsy 12 Hour Cold Caplets, Robitussin Cold Severe Congestion Capsules, Sudafed 24 Hour Tablets, Triaminic Cold and Cough Liquid, Thera-Flu Cold and Cough Hot Liquid, Tylenol Sinus Severe Congestion Caplets, and Vicks 44M Cough, Cold and Flu Relief. Numerous case reports3,4 in the literature suggest that oral sympathomimetic agents can raise blood pressure (BP) to dangerous levels, whereas other reviews5,6 suggest that the danger from these medications is exaggerated. In November 2000, the US Food and Drug Administration recommended that medications that contain phenylpropanolamine be voluntarily recalled because of concern regarding an increased incidence of hemorrhagic stroke.7 Markedly elevated BPs have been noted in conjunction with phenylpropanolamine-associated strokes, and hypertension has been suggested as a possible mechanism of drug toxicity.8 Because physicians commonly prescribe pseudoephedrine to relieve the symptoms of the common cold, they speculate about its safety, particularly in patients with hypertension. In addition, because sympathomimetic agents can potentially elevate the heart rate (HR), safety issues also arise in patients with conditions such as atrial fibrillation, in which alterations in HR control could potentially result in harm. Our purpose is to conduct a systematic review of the literature to determine the effect of oral pseudoephedrine, used in adults, on HR and BP. Our a priori subgroup analytic questions included the following: Are the magnitude of changes on HR and BP affected by patient characteristics, such as age, sex, and currently treated hypertension, or by drug characteristics, such as extended- or immediate-release formulations, dose, and treatment duration?