Information on the long-term health of living liver donors is incomplete. Because changes in standard laboratory tests may reflect the underlying health of donors, results before and after donation were examined in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). A2ALL followed 487 living liver donors who donated at 9 US transplant centers between 1998 and 2009. The aminotransferase [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and alkaline phosphatase (AP) activities, bilirubin, international normalized ratio (INR), albumin, white blood cell count (WBC), hemoglobin (HGB), platelet count, ferritin, serum creatinine (SCR), and blood urea nitrogen (BUN) were measured at the evaluation and after donation (1 week, 1 month, 3 months, 1 year, and yearly thereafter). Repeated measures models were used to estimate median laboratory values at each time point and to test for differences between values at the evaluation (baseline) and postdonation time points. Platelet counts were significantly decreased at every time point in comparison with the baseline, and at 3 years, they were 19% lower. Approximately 10% of donors had a platelet count < 150 × 1000/mm(3) 2 to 3 years post-donation. Donors with a platelet count ≤ 150 × 1000/mm(3) at 1 year had significantly lower mean platelet counts (189 ± 32 × 1000/mm(3) ) versus the remainder of the cohort (267 ± 56 × 1000/mm(3) , P < 0.0001) at the evaluation. Statistically significant differences compared to the evaluation values were noted for AST, AP, INR, and albumin through the first year, although most measurements were in the normal range. The median values for WBC, HGB, ferritin, albumin, SCR, BUN, and INR were not substantially outside the normal range at any time point. In conclusion, after 3 months, most laboratory values return to normal among right hepatic lobe liver donors, with a slower return to baseline levels for AST, AP, INR, and albumin. Persistently decreased platelet counts warrant further investigation.