Objectives: Measurements of protein content, enzymatic activity, and/or capillarization are frequently utilized as markers of skeletal muscle adaptation following exercise training. Whether changes in these markers of muscle adaptation are repeatable when individuals are repeatedly exposed to the same training stimulus is unknown. The purpose of this study was to test the repeatability of skeletal muscle adaptations to two identical training periods. Methods: Ten active young males (age: 22 +/- 2 years; VO(2)max: 57 +/- 7 ml/kg/min) were exposed to two identical four-week periods of supervised high-intensity interval running (4 x 4 min at 90-95% of HRmax interspersed with 3-min at 70-75% HRmax) separated by a 3-month wash-out period. Vastus lateralis biopsies were obtained before and after each training period for the measurement of protein content, enzyme activity, and capillary density. Results: Training-induced changes in citrate synthase (CS) maximal activity, protein content (PGC-1 alpha, OXPHOS, and LDH-A), and capillary density were not repeatable within individuals (r = -0.52-0.15; ICCs: -0.42-0.04; CVs: 11-67%). Several OXPHOS complex subunits also demonstrated dissimilar group-level adaptations (period x time interaction effects, p < 0.05) with large differences (eta(2)(p) > 0.4) between training periods. A large (eta(2)(p) = 0.65) increase in capillary density was apparent irrespective of training period (main effect of time, p = 0.05). Conclusions: An individual (or a group of individuals) may exhibit dissimilar skeletal muscle adaptations when re-exposed to the same training stimulus. Our findings challenge the utility of classifying of individuals as high/low responders using measurements of mitochondrial protein content, CS activity and/or capillary density following a single training period. (C) 2020 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.