Background: Vulvodynia is an unexplained chronic vulvar pain condition. Case-control studies provide opportunities to examine potential mechanisms by which vulvodynia may develop. Findings inform etiological models that can be tested in subsequent prospective studies. Methods: A survey of interpersonal relationships and the Structured Clinical Interview for DSM-IV Axis I Disorders was administered to 215 case-control pairs of women with and without vulvodynia. Conditional logistic regression was used to examine associations between affect-based chronic stressors (i.e., living in fear of abuse, perceived abuse, and antecedent mood disorders) with vulvodynia. These associations were then examined among women with and without a history of childhood abuse. Results: Among women with a history of severe childhood abuse, those with vulvodynia had three times the odds of living in fear of any abuse compared to women without vulvodynia (95% confidence interval: 1.0, 11.0), after adjustment for childhood poverty. Among women with no history of childhood abuse, those with vulvodynia had over six times the odds of antecedent mood disorder compared to women without vulvodynia (95% confidence interval: 1.9,19.6). Conclusion: Our findings suggest that affect-based chronic stressors may be important to the psychobiological mechanisms of vulvodynia. Prospective studies are recommended to test biopsychosocial models of the etiology of vulvodynia.