We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In normotensive pregnancy (n=142), we found that from the beginning of pregnancy to delivery, UACR increased by a median (interquartile range (IQR)) of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) (p<0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in the absence of hypertension) was identified in 19 /142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery, and increases in UACR from early to mid-pregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early and mid-pregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a 'microalbuminuric' phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared to women with preeclampsia, where proteinuria has a more abrupt onset.