BackgroundFace-to-face cognitive–behavioural therapy (CBT) leads to a reduction of fatigue in chronic fatigue syndrome (CFS).AimsTo test the efficacy of internet-based CBT (iCBT) for adults with CFS.MethodA total of 240 patients with CFS were randomised to either iCBT with protocol-driven therapist feedback or with therapist feedback on demand, or a waiting list. Primary outcome was fatigue severity assessed with the Checklist Individual Strength (Netherlands Trial Register: NTR4013).ResultsCompared with a waiting list, intention-to-treat (ITT) analysis showed a significant reduction of fatigue for both iCBT conditions (protocol-driven feedback: B = −8.3, 97.5% CI −12.7 to −3.9, P < 0.0001; feedback on demand: B = −7.2, 97.5% CI −11.3 to –3.1, P < 0.0001). No significant differences were found between both iCBT conditions on all outcome measures (P = 0.3–0.9). An exploratory analysis revealed that feedback-on-demand iCBT required less therapist time (mean 4 h 37 min) than iCBT with protocol-driven feedback (mean 6 h 9 min, P < 0.001) and also less than face-to-face CBT as reported in the literature.ConclusionsBoth iCBT conditions are efficacious and time efficient.Declaration of interestNone.