The purpose of this study was to determine the effect of long-term Cr supplementation on blood parameters reflecting liver and kidney function. Twenty-three members of an NCAA Division II American football team (ages = 19–24 years) with at least 2 years of strength training experience were divided into a Cr monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously ingested creatine, and a control group (n = 13) in which they took no supplements. Individuals in the CrM group averaged regular daily consumption of 5 to 20 g (mean ± SD = 13.9 ± 5.8 g) for 0.25 to 5.6 years (2.9 ± 1.8 years). Venous blood analysis for serum albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine produced no significant differences between groups. Creatinine clearance was estimated from serum creatinine and was not significantly different between groups. Within the CrM group, correlations between all blood parameters and either daily dosage or duration of supplementation were nonsignificant. Therefore, it appears that oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements.