Aim Muscle fibre hypertrophy is accompanied by an increase in myonuclear number, an increase in myonuclear domain size or both. It has been suggested that increases in myonuclear domain size precede myonuclear accretion and subsequent muscle fibre hypertrophy during prolonged exercise training. In this study, we assessed the changes in muscle fibre size, myonuclear and satellite cell content throughout 12 weeks of resistance‐type exercise training in young men. Methods Twenty‐two young men (23 ± 1 year) were assigned to a progressive, 12‐weeks resistance‐type exercise training programme (3 sessions per week). Muscle biopsies from the vastus lateralis muscle were taken before and after 2, 4, 8 and 12 weeks of exercise training. Muscle fibre size, myonuclear content, myonuclear domain size and satellite cell content were assessed by immunohistochemistry. Results Type I and type II muscle fibre size increased gradually throughout the 12 weeks of training (type I: 18 ± 5%, type II: 41 ± 6%, P < 0.01). Myonuclear content increased significantly over time in both the type I (P < 0.01) and type II (P < 0.001) muscle fibres. No changes in type I and type II myonuclear domain size were observed at any time point throughout the intervention. Satellite cell content increased significantly over time in both type I and type II muscle fibres (P < 0.001). Conclusion Increases in myonuclear domain size do not appear to drive myonuclear accretion and muscle fibre hypertrophy during prolonged resistance‐type exercise training in vivo in humans.