It is widely appreciated by the medical community that subtle deficits in intellect, academic skills and executive functioning exist in early treated phenylketonuria (PKU). In this study, we described the relationship between intellectual outcome and concentration/variation in blood phenylalanine (Phe) during specific developmental periods (0-5 years, 6-10 years, >10 years). We also examined the association between mean number of blood Phe samples and maintenance of Phe within treatment range (120-360 ìmol/L) and within one standard deviation (SD) of index of dietary control, defined as the mean of 12-month median Phe. Retrospective data was collected from 55 patients receiving treatment at the University of Utah Metabolic Clinic. Index of dietary control (IDC) and SD blood Phe steadily increased and mean number of samples decreased during each developmental period. The correlation between IDC during 6-10 years of life and perceptual reasoning was -.370 (p = 0.006). Using multivariate linear regression, IDC during 0-5 years and 6-10 years were associated with a 0.5-point decrease and 0.3-point decrease in perceptual reasoning scores for every 100 ìmol/L increase in blood Phe, though associations were nonsignificant (p = 0.067; 0.082). SD of Phe was not associated with any measure of intelligence. The likelihood of IDC >360 ìmol/L in those 6-10 years was 32.3% lower for each additional blood Phe sample per year (p = 0.001). The present study suggests frequent blood Phe monitoring during ages 6-10 years may reduce blood Phe and prevent deficits in perceptual reasoning later in life.