Context: Evidence concerning the determinants of vaginismus (V), in particular medical conditions, is inconclusive. Objective: To investigate, in a cohort of subjects consulting for female sexual dysfunction, whether there is a difference in medical and psychosocial parameters between women with V and women with other sexual complaints. Methods: A series of women attending our clinic for female sexual dysfunction (FSD) was retrospectively studied. V was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria (DSM-IV-TR). Patients: A series of 255 women with FSD was consecutively recruited. V was diagnosed in 20 patients (7.8%). Lifelong and acquired V cases were included. Interventions: Retrospective analysis of the patients, who underwent physical and biochemical examination. Furthermore they completed some validated questionnaires and underwent clitoral ultrasound examination. Main Outcome Measures: Patients underwent a structured interview and physical, gynecologic, laboratory, and clitoral ultrasound examinations; they completed the Female Sexual Function Index (FSFI), the Middlesex Hospital Questionnaire, the Female Sexual Distress Scale Revised (FSDS), and the Body Uneasiness Test (BUT). Results: Women with V were significantly younger than the rest of the sample (p < 0.05). No differences were found for traditional risk factors such as a history of sexual abuse, relational parameters, or gynecologic diseases or for newly investigated parameters (i.e., neurologic, hormonal, and metabolic alterations). Women with V showed significantly higher histrionic-hysterical symptoms and traits (as detected by MHQ-H score; p < 0.05) compared with subjects with other sexual complaints. When the scores of all MHQ subscales were simultaneously introduced in a logistic model, the association between V and MHQ-H score was confirmed (P=0.13). Women with V also showed higher FSFI pain and FSDS total scores, even after adjusting for age (p < 0.05). In an age-adjusted model, FSDS total score increased as a function of the years of duration of V but not as a function of its severity. All observations were confirmed in a case-control study (ratio=1:3). Conclusions: V was associated with histrionic-hysterical traits, FSFI pain domain, and sex-related distress. A history of abuse, relational parameters, gynecologic diseases, and hormonal and metabolic alterations do not seem to play a role in the development of V.