Background: Adolescents consume more sugar-sweetened beverages than do individuals in any other age group, but it is unknown how the type of sugar-sweetened beverage affects metabolic health in this population. Objective: The objective was to compare the metabolic health effects of short-term (2-wk) consumption of high-fructose (HF) and high-glucose (HG)-sweetened beverages in adolescents (15-20 y of age). Design: In a counterbalanced, single-blind fashion, 40 male and female adolescents completed two 2-wk trials that included 1) an HF trial in which they consumed 710 mL of a sugar-sweetened beverage/d (equivalent to 50 g fructose/d and 15 g glucose/d) for 2 wk and 2) an HG trial in which they consumed 710 mL of a sugar-sweetened beverage/d (equivalent to 50 g glucose/d and 15 g fructose/d) for 2 wk in addition to their normal ad libitum diet. In addition, the participants maintained similar physical activity levels during each trial. The day after each trial, insulin sensitivity and resistance [assessed via Quantitative Insulin Sensitivity Check Index (QUICKI) and homeostatic model assessment of insulin resistance (HOMA-IR) index] and fasting and postprandial glucose, lactate, lipid, cholesterol, insulin, C-peptide, insulin secretion, and clearance responses to HF or HG mixed meals were assessed. Results: Body weight, QUICKI (whole-body insulin sensitivity), HOMA-IR (hepatic insulin resistance), and fasting lipids, cholesterol, glucose, lactate, and insulin secretion or clearance were not different between trials. Fasting HDL- and HDL3-cholesterol concentrations were ∼10-31% greater (P < 0.05) in female adolescents than in male adolescents. Postprandial triacylglycerol, HDL-cholesterol, HDL3-cholesterol, and glucose concentrations were not different between HF and HG trials. The lactate incremental area under the curve was ∼3.7-fold greater during the HF trial (P < 0.05), whereas insulin secretion was 19% greater during the HG trial (P < 0.05). Conclusions: Moderate amounts of HF- or HG-sweetened beverages for 2 wk did not have differential effects on fasting or post-prandial cholesterol, triacylglycerol, glucose, or hepatic insulin clearance in weight-stable, physically active adolescents. This trial was registered at clinicaltrials.gov as NCT02058914.