Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska. We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis. ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001). A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons.