The occurrence of cardiovascular side effects is sometimes associated with the utilization of β-adrenoceptor agonists. The most important causes of these undesirable pharmacologic actions are as follows: (1) direct stimulation of cardiac β-adrenoceptors; (2) reflex activation of adrenergic mechanisms due to peripheral vasodilation; (3) hypokalemia; and (4) hypoxemia. The aim of this study was to evaluate the potential short-term, cardiovascular side effects of salmeterol, a long-acting and highly selective β2-adrenoceptor agonist. Eight volunteer healthy subjects and eight patients with reversible airway obstruction and without cardiovascular alterations were treated with 50 µg of salmeterol twice a day for 3 days and then with 100 µg of salmeterol twice a day for a further 3-day period. The 24-h ECG (Holter) monitoring and measurement of arterial BP, performed on the admission day and on the third and the sixth day of pharmacologic treatment, showed that salmeterol did not produce any significant change in mean heart rate, number of supraventricular and ventricular premature complexes, and BP. Furthermore, no ECG abnormality related to myocardial ischemia was recorded during 24-h Holter monitoring. These data suggest that salmeterol, administered in regular and high doses for a short period, does not cause significant cardiovascular effects in both normal subjects and patients with reversible airway obstruction.