Oral pseudoephedrine is commonly used to treat symptoms of rhinitis and rhinorrhea, but its effect on blood pressure (BP) and heart rate (HR) remains uncertain. We assessed whether pseudoephedrine causes clinically meaningful elevations in HR or BP. We searched MEDLINE, EMBASE, and the Cochrane Library for English-language, randomized placebo-controlled trials of oral pseudoephedrine treatment in adults. The primary data extracted were systolic BP (SBP), diastolic BP (DBP), and HR. Study quality was assessed using the methods of Jadad, and data were synthesized using a random-effects model and weighted mean differences. Twenty-four trials had extractable vital sign information (45 treatment arms; 1285 patients). Pseudoephedrine caused a small but significant increase in SBP (0.99, mm Hg; 95% CI, 0.08 to 1.90) and HR (2.83 beats/min; 95% CI, 2.0 to 3.6), with no effect on DBP (0.63 mm Hg, 95% CI, -0.10 to 1.35). The effect in patients with controlled hypertension demonstrated an SBP increase of similar magnitude (1.20 mm Hg; 95% CI, 0.56 to 1.84 mm Hg). Higher doses and immediate-release preparations were associated with greater BP increases. Studies with more women had less effect on BP or HR. Shorter duration of use was associated with greater increases in SBP and DBP.