In hemodialysis patients with secondary hyperparathyroidism (SHPT) ultrasonography of the parathyroid glands allows to assess the glandular growth and to define the limits of medical treatment. The present retrospective study evaluated the relationship between parathyroid gland hyperplasia and the effectiveness of new drugs. Fifty-three patients with SHPT (iPTH > 400 pg/mL) after treatment with oral calcitriol were included in the study. These patients underwent parathyroid ultrasonography and sequential therapy with intravenous calcitriol (first step), paracalcitol (second step), and paracalcitol + cinacalcet (third step). Patients with median PTH < 300 pg/mL during the period of therapy and follow-up were considered responders. The therapeutic response was correlated with ultrasound parameters (number of parathyroid glands, maximum longitudinal diameter, structural score, and vascular score). Four (10%) of 41 patients treated with IV calcitriol, 7 (27%) of 26 patients treated with paracalcitol, 7 (41%) of 17 patients treated with cinacalcet and paracalcitol, and 1 (20%) of 5 patients treated with cinacalcet alone were responders. ROC curve analysis showed that maximum longitudinal diameter (< 9 mm), number of parathyroid glands (< -1), structural score (< 2), and vascular score (< 2) predicted response to any treatment. New drugs (paracalcitol, cinacalcet) are more effective in SHPT than conventional ones. However, the traditional ultrasonographic cutoff for the efficacy of medical therapy remained unchanged. Thus parathyroid gland ultrasonography predicts the therapeutic response also to the new drugs.