Objective: To determine 1) the association between maternal history of fibroids and fibroids in women under the age of 50 and 2) the ability of subjects to report family history of fibroids.Design: We performed a hospital-based case-control study with cases being women found to have pathologically confirmed fibroids and controls being women with no fibroids after pathologic examination of the uterus or by transvaginal ultrasonography.Materials/Methods: All women were sent a questionnaire that included 52 items regarding medical history, reproductive history, social history, family history and demographic information. Dichotomous variables were compared by Fisher’s exact test, categorical variables by Pearson’s chi-square and continuous variables by both the t test and the Wilcoxon rank-sum test. Univariate logistic regression was used to assess each potential risk factor in predicting case-control status. Those variables deemed clinically important or that were significant by univariate analysis were entered into a multiple logistic regression for the purpose of attaining the final model.Results: 81 of 169 (47.9%) cases and 103 of 214 (48.1%) of controls completed the questionnaire. By multiple logistic regression, significant risk factors for the presence of fibroids were maternal history of fibroids (odds ratio = 2.85, confidence intervals 1.25–6.52) and reduced parity (odds ratio = 0.75, confidence intervals 0.57–0.98). The protective effect of parity increased linearly to the number of children. Increasing age before the age of 50 was nearly significant as a risk factor (odds ratio = 1.07, confidence intervals 1.00–1.15). Cases with a positive maternal history of fibroids tended to be younger when the fibroids were first diagnosed as compared to cases with no maternal history of fibroids (38 versus 42.5 years, p = 0.14). 24% of subjects did not know the maternal history of fibroids, while 29% and over 50% were not aware of this history in a sister or grandmother, respectively. Extended family histories of fibroids could not be ascertained by this questionnaire-based study.Conclusions: Our results suggest that a maternal history of fibroids may be the biggest risk factor for development of fibroids in a largely Caucasian population of women. Further studies are needed to better understand the possible genetic contribution to the development of uterine fibroids. Given the ascertainment bias inherent in second-hand maternal histories, future studies should assess maternal fibroid presence by ultrasonographic or pathologic evaluation. Objective: To determine 1) the association between maternal history of fibroids and fibroids in women under the age of 50 and 2) the ability of subjects to report family history of fibroids. Design: We performed a hospital-based case-control study with cases being women found to have pathologically confirmed fibroids and controls being women with no fibroids after pathologic examination of the uterus or by transvaginal ultrasonography. Materials/Methods: All women were sent a questionnaire that included 52 items regarding medical history, reproductive history, social history, family history and demographic information. Dichotomous variables were compared by Fisher’s exact test, categorical variables by Pearson’s chi-square and continuous variables by both the t test and the Wilcoxon rank-sum test. Univariate logistic regression was used to assess each potential risk factor in predicting case-control status. Those variables deemed clinically important or that were significant by univariate analysis were entered into a multiple logistic regression for the purpose of attaining the final model. Results: 81 of 169 (47.9%) cases and 103 of 214 (48.1%) of controls completed the questionnaire. By multiple logistic regression, significant risk factors for the presence of fibroids were maternal history of fibroids (odds ratio = 2.85, confidence intervals 1.25–6.52) and reduced parity (odds ratio = 0.75, confidence intervals 0.57–0.98). The protective effect of parity increased linearly to the number of children. Increasing age before the age of 50 was nearly significant as a risk factor (odds ratio = 1.07, confidence intervals 1.00–1.15). Cases with a positive maternal history of fibroids tended to be younger when the fibroids were first diagnosed as compared to cases with no maternal history of fibroids (38 versus 42.5 years, p = 0.14). 24% of subjects did not know the maternal history of fibroids, while 29% and over 50% were not aware of this history in a sister or grandmother, respectively. Extended family histories of fibroids could not be ascertained by this questionnaire-based study. Conclusions: Our results suggest that a maternal history of fibroids may be the biggest risk factor for development of fibroids in a largely Caucasian population of women. Further studies are needed to better understand the possible genetic contribution to the development of uterine fibroids. Given the ascertainment bias inherent in second-hand maternal histories, future studies should assess maternal fibroid presence by ultrasonographic or pathologic evaluation.