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Objective: The purpose of this study was to compare gestational trophoblastic disease incidence rates with the use of population-based data., Study Design: All incident cases between 1973 and 1997 and live birth, pregnancy, and women at risk were tabulated with the use of data that were derived from the New Mexico Tumor Registry and Vital Records and Health Statistics Annual Reports. Statistical methods included trends analyses, odds ratios, and Poisson regression., Results: Of 939 total cases, 312 non-Hispanic white women, 399 Hispanic white women, 201 American Indian women, and 27 other women were affected. Age-adjusted incidence rates were significantly higher for American Indian women (11.16%) compared with non-Hispanic (3.57%) or Hispanic white women (5.32%); the probability value was <.001. When live birth (1:438 women) and pregnancy (1:486 women) denominators were considered, American Indian women alone were at increased risk, and the ratio increased by 56% over 25 years. American Indian women were also at increased risk for partial mole (relative risk, 4.03; 95% CI, 2.57-6.31), invasive mole (relative risk, 26.7; 95% CI, 7.81-93.14), and choriocarcinoma (relative risk, 6.29; 95% CI, 1.81-22.66) variants., Conclusion: American Indians are at increased risk relative to the other predominant ethnic groups in New Mexico. Age-adjusted standardization provided a reproducible measurement that may be applicable across other registries.