The aim of the study was to assess workload capacity and blood pressure (BP) response to treadmill exercise and 24-hour BP monitoring in children with Williams syndrome. Seventeen children were examined (8 males and 9 females) whose mean age was 13.8 ± 3.6 years. Six patients were on antihypertensive therapy. Each patient underwent clinical examination and measurement of BP at rest, during exercise, and during 24-hour monitoring. Two-dimensional echocardiogram and echo-Doppler of renal arteries were performed. The test was stopped for muscular fatique or reduced cooperation. The patients, when compared to a population of healthy children, had reduced total time of exercise (7.3 ± 1.9 vs 14.3 ± 2.6 min, p < 0.001) and, at the same workload, increased heart rate (167 ± 19 vs 145 ± 16 beats/min, p < 0.001) and increased maximum systolic BP (146 ± 27 vs 128 ± 12 mmHg, p = 0.01). Ambulatory blood pressure measurement values showed higher systolic blood pressure both during daytime and nighttime. Our study confirms that children and adolescents with Williams syndrome are at high risk for hypertension, probably related to the alterations of large arteries. The data relating to the synthesis of elastin may have a direct relationship to the compliance of the arterial system, leading to hypertension.