One thousand eleven patients with essential hypertension (H) were evaluated upon compliance with the following inclusion criteria: (a) mild to moderate uncomplicated H, with supine diastolic blood pressure (Su DBP) greater than 90 mm Hg at the end of the placebo period, with or without antihypertensive treatment; (b) greater than 20 years old. The dosage of ketanserin (K) was 20 mg b.i.d. up to the fourth week. Afterwards, if the patients normalized, we continued with the same schedule. If this did not occur, the dosage was increased (40 mg b.i.d.) up to the eighth week. Four hundred fifty-one men and 560 women were included, with a mean age of 56.6 years, mean body weight 74.8 kg, and mean height 166.30 cm. At the end of the eighth week, the percentage of normalization was 75.5% of the patients, and the percentage of partial responders was 5.6%. The decrease of the blood pressure (diastolic and systolic) was significant at the second week (paired t test, two-tailed probability, p less than or equal to 0.001). There were 62 dropouts: 10 due to inefficacy, 14 due to adverse reaction, and 38 due to other reasons. Laboratory examinations were performed before and after treatment and did not show statistical differences. Also, a 12-lead ECG was performed before and after treatment with K. The QTc was analyzed in a sample of 140 patients and did not show statistically significant changes. The incidence of side effects was minimal (24% of the patients, n = 224), mild, and transient; only 1% of the patients dropped out due to adverse reactions. In our experience, ketanserin was an effective and safe drug, to be used primarily for the treatment of mild to moderate H.