Purpose: Demarcated primary second molar hypomineralization (DMH-Es) is a common developmental defect of enamel, with prevalence estimates between five percent and 20 percent. From the Americas, studies exploring the problem of DMH-Es and explicitly using the European Academy of Pediatric Dentistry diagnostic criteria were limited to some South American countries, but no similar studies were available from any of the North American countries including the United States. The purpose of this study was to investigate the prevalence and sociodemographic determinants of DMH-Es among schoolchildren in Indiana, USA. Methods: Four hundred twenty-three schoolchildren (average age equals 7.6 [±2.2 standard deviation] years) were examined by a calibrated pediatric dentist. Sociodemographic data were collected from patients' questionnaires and electronic dental records. Results: DMH-Es had a prevalence estimate of six percent versus 40 percent overall of any enamel defect (AED) of the primary second molars (PSMs) and/or the permanent first molars (PFMs). Race/ethnicity was significantly associated with a higher overall prevalence of AED of PSMs but not with the prevalence estimate of DMH-Es. Older age group (10 years or older), living in central Indiana, and water fluoridation were significantly associated with a higher overall prevalence of AEDs (P<0.01) but not with the prevalence of DMH-Es. Caries experience was significantly higher in children with demarcated molar hypomineralization (DMH) of PFMs and/or PSMs than in the group without. Conclusions: DMH-Es prevalence estimate was similar to the global figures. Certain demographic characteristics were significantly associated with the overall prevalence of the enamel defects of the examined teeth.