The aim of the study is to evaluate the effectiveness of phalangeal quantitative ultrasound (QUS) in monitoring the treatment with raloxifene or estrogen-progestogens in postmenopausal women attending an Italian Menopause Centre. Caucasian women (n = 268) were enrolled in the study and underwent annual check-ups between October 1998 and October 2004. All were measured with the IGEA DBM Sonic Bone Profiler (BP) at the startup of treatment and in the following years. Three groups were identified: subjects not receiving treatment (n = 144), subjects treated with raloxifene (n = 53) and subjects treated with estrogen-progestogens (n = 71). The three analyzed groups were similar for age, weight and menopausal age. A significant decrease in amplitude-dependent speed of sound (AD-SoS) and Ultrasound Bone Profile Index (UBPI; p < 0.05) was observed in the nontreated group, whereas a positive effect in treated groups could be evidenced in the follow-up. In particular, a significant positive effect (p < 0.05) on AD-SoS corrected for age in the group treated with raloxifene has been observed, whereas in the group treated with estrogen-progestogens a nonsignificant positive effect on AD-SoS corrected for age was observed. The absolute AD-SoS value was maintained over the years of follow-up. The UBPI data show a slowing down of the bone loss in the treated groups, especially in the raloxifene group, in contrast with the significant decrease in the nontreated group. The result of this study shows the DBM Sonic Bone Profiler is an efficient device to monitor the effects of treatment, not only in the strict control settings of clinical trials, but also in clinical practice.