In this study, 431 consecutive patients with mitral valve prolapse (MVP) diagnosed by two-dimensional echocardiography were employed to further investigate the site-related difference in the prevalence of MVP. Following echocardiographic determination of the site and severity of MVP, a pulsed-Doppler technique was further performed to assess the existence and severity of mitral regurgitation (MR) in all patients. These patients were then classified by age in 10-year groups with patients older than 60 years being enrolled in one group. The younger groups accounted for a large number of the patients with MVP in our study, with the number of patients being reduced with age. In addition, female patients tended to predominate up until the 50s, but not in the 50 and older groups. The prevalence of MVP at the centro-medial site of the anterior mitral leaflet (AML) predominated in all age groups, gradually decreasing with age, except for a peak in the 40s, before continuing to decline in the 50 and older groups. On the other hand, the prevalence of MVP at the lateral site of the AML and at the posterior mitral leaflet (PML) increased with age. In the 50 and older age groups, the prevalence of MVP at these sites increased steeply with age. However, the prevalence of MVP at both the lateral site of the AML and PML did not significantly increase with age. The trend shown above was not significantly different for gender. The number of patients with MR increased with age independent of the site of MVP. However, the prevalence and severity of MR associated with MVP at the lateral site of the AML and/or at the PML were significantly greater than at the other sites up until the 50s (p<0.05). When patients were older than 50 years, this significant site-related difference in the prevalence of MR was not observed because of the higher prevalence of MR in the older patients in this study. Forty-one patients could be followed for 2 to almost 5 years. Three of the 41 patients were observed to have MVP at the centro-medial site of the AML in the initial examination, but the site of MVP had extended to the lateral side of the AML in the final examination. Two patients with MVP at all 3 sites of the AML demonstrated an increase in the severity of MVP. However, there were no newly documented cases of MR among those patients. These findings suggested that 1) different causes relating to the site of the mitral valve are exerted to create MVP, 2) it is clinically important to consider the greater prevalence and severity of MR associated with MVP of the lateral site of the AML and/or the PML when MVP involves these sites even though minimum changes in the valvular lesions are observed, 3) it should be noted in the majority of MVPs at the centro-medial site of the AML, that follow-up patients will have the same site and severity of MVP at the final examination; however, for some patients where MVP initially appeared at the centro-medial site of the AML, there will be newly extended MVP to other sites, indicating deteriorating prognosis of MVP.