Endometriosis is a chronic inflammatory disease, which is especially found in women with subfertility problems with an incidence of up to 30%. The disease is considered an estrogen-dependent disorder, where DNA polymorphisms of the estrogen receptor alpha (ERalpha) in connection with endometriosis are controversially discussed. From a German population of women, clinical data associated with the disease, including the American Fertility Society (AFS) I-IV classification, and non-clinical parameters were evaluated statistically in endometriosis patients (n = 98) and in control women (n = 98) without endometriosis. Using a multivariate statistical analysis, significant associations of endometriosis with dysmenorrhea (P < 0.001) and allergies against medicaments (P = 0.042) were found. A positive trend between first grade family history of endometriosis and allergies against medicaments was also observed, suggesting a genetic relationship. From both collectives, DNA from peripheral blood was analyzed for the frequency of the ERalpha DNA polymorphisms Xba1 (A/G) and PvuII (T/C) in intron 1 and the ERalpha exonic DNA polymorphism (G229A) with an amino acid exchange (Gly77Ser) in the transactivation domain. DNA samples from endometriosis lesions and control tissues from the same collectives were also analyzed for the exonic G229A polymorphism. Only homozygote wild-type alleles for the polymorphism G229A were found, making it a rare polymorphism in mid-European individuals. Allele types for the PvuII and Xba1 polymorphisms were analyzed with the observed statistically significant clinical parameters and showed no significant association with endometriosis; however a trend with AFS IV was noted, which could contribute to lesion severity. In conclusion, the analyzed polymorphisms in the ERalpha do not have a functional role concerning specific clinical parameters associated with endometriosis.