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Routine childhood varicella vaccination, implemented in 1995, has resulted in significant declines in varicella-related hospitalizations in the United States. Varicella hospitalization rates among the American Indian (AI) and Alaska Native (AN) population have not been previously documented.We selected varicella-related hospitalizations, based on a published definition, from the Indian Health Service inpatient database for AI/ANs in the Alaska, Southwest and Northern Plains regions (1995–2010) and from the Nationwide Inpatient Sample for the general US population (2007–2010). We analyzed average annual hospitalization rates prevaccine (1995–1998) and postvaccine (2007–2010) for the AI/AN population, and postvaccine for the general US population.From 1995–1998 to 2007–2010, the average annual varicella-related hospitalization rate for AI/ANs in the 3 regions decreased 95% (0.66–0.03/10,000 persons); the postvaccine rate appears lower than the general US rate (0.06, 95% confidence interval: 0.05–0.06). The rate declined in all AI/AN pediatric age groups. Infants experienced the highest prevaccine (14.07) and postvaccine (0.83) hospitalization rates. Adults experienced low rates in both periods. Varicella vaccination rates in 19- to 35-month-old AI/AN children during fiscal years 2008–2010 were 88.1–91.0%.Widespread use of varicella vaccine in AI/AN children was accompanied by substantial declines in varicella-related hospitalizations consistent with high varicella vaccine effectiveness in preventing severe varicella outcomes.