Background: This study compared the best available treatment for bulimia nervosa, cognitive-behavioural therapy (CBT) augmented by fluoxetine if indicated, with a stepped-care treatment approach in order to enhance treatment effectiveness. Aims: To establish the relative effectiveness of these two approaches. Method: This was a randomised trial conducted at four clinical centres (Clinicaltrials.gov registration number: NCT00733525). A total of 293 participants with bulimia nervosa were randomised to one of two treatment conditions: manual- based CBT delivered in an individual therapy format involving 20 sessions over 18 weeks and participants who were predicted to be non-responders after 6 sessions of CBT had fluoxetine added to treatment; or a stepped-care approach that began with supervised self-help, with the addition of fluoxetine in participants who were predicted to be non-responders after six sessions, followed by CBT for those who failed to achieve abstinence with self-help and medication management. Results: Both in the intent-to-treat and completer samples, there were no differences between the two treatment conditions in inducing recovery (no binge eating or purging behaviours for 28 days) or remission (no longer meeting DSM-IV criteria). At the end of 1-year follow-up, the stepped-care condition was significantly superior to CBT. Conclusions: Therapist-assisted self-help was an effective first-level treatment in the stepped-care sequence, and the full sequence was more effective than CBT suggesting that treatment is enhanced with a more individualised approach.