Hypertrophy of developing skeletal muscle involves stimulation by insulin-like growth factor-I (IGF-I), however, the role of IGF-I in adult muscle is less clarified. In the present study, the mRNA splice variants of IGF-I (IGF-IEa and MGF) and the changes in muscle fiber cross sectional area after 12weeks of training were studied in elderly post-operative patients. About 28 subjects, 14 men and 14 women (age 69, range 60-86 years) were randomized to unilateral resistance training (RT: 3/week), electrical stimulation (ES: 1h/day) or functional exercises (FE: 1h/day). The non-operated-side served as a within subject control. Muscle biopsies were obtained from the vastus lateralis of both limbs at +2d post-operative (baseline), at 5weeks and 12weeks post-surgery to analyze for changes in type 1 and type 2 muscle fiber area. Changes in expression levels of IGF-I mRNA isoforms were determined using real-time RT-PCR, normalized to the ribosomal protein large protein 0 (RPLP0) mRNA and presented relative to the control-side. At baseline there was no difference between the three groups in muscle fiber area or resting levels of IGF-IEa and MGF. RT resulted in a significant increase in muscle fiber area of type 1 (+17%, p<0.05) and type 2 (+36%, p<0.05) parallel to an increase in the expression of IGF-IEa and MGF, in contrast to ES and FE. The present study demonstrates that resistance training initiated in the acute post-operative phase is highly effective in increasing mean fiber area and in addition induces marked increases in the expression of IGF-I splice variants, supporting the idea that IGF-I is involved in regulating muscle hypertrophy.