The aim of this study was to investigate the long term efficacy of family-focused cognitive behaviour therapy (CBT) compared with psycho-education in improving school attendance and other secondary outcomes in adolescents with chronic fatigue syndrome (CFS). A 24 month follow-up of a randomised controlled trial was carried out. Participants received either 13 one-hour sessions of family-focused CBT or four one-hour sessions of psycho-education. Forty-four participants took part in the follow-up study. The proportion of participants reporting at least 70% school attendance (the primary outcome) at 24 months was 90% in CBT group and 84% in psycho-education group; the difference between the groups was not statistically significant (OR = 1.29, p = 0.80). The proportion of adolescents who had recovered in the family-focused CBT group was 79% compared with 64% in the psycho-education, according to a definition including fatigue and school attendance. This difference was not statistically significant (Fisher's exact test, p = 0.34). Family-focused CBT was associated with significantly better emotional and behavioural adjustment at 24 month follow-up compared to psycho-education, as reported by both adolescents (F = 6.49, p = 0.02) and parents (F = 4.52, P = 0.04). Impairment significantly decreased in both groups between six and 24 month follow-ups, with no significant group difference in improvement over this period. Gains previously observed for other secondary outcomes at six month follow-up were maintained at 24 month follow-up with no further significant improvement or group differences in improvement. In conclusion, gains achieved by adolescents with CFS who had undertaken family-focused CBT and psycho-education generally continued or were maintained at two-year follow-up. The exception was that family-focused CBT was associated with maintained improvements in emotional and behavioural difficulties whereas psycho-education was associated with deterioration in these outcomes between six and 24-month follow-up. ► Adolescents with CFS received either family-focused CBT or psycho-education. ► At 24 month follow-up, school attendance improvements were maintained in both groups. ► Impairment reduced further in both groups between six and 24-month follow-ups. ► Emotional and behavioural difficulties were lower in the CBT group at 24 months. ► Improvements in other outcomes were maintained in both groups at 24 months.