Twenty-three double blind, randomized, multiple crossover trials (N-of-1 RCT) of amitriptyline were conducted in patients with fibromyalgia. The benefit of amitriptyline was assessed using a symptom questionnaire and count of tender points. To assess the usefulness of the method, the proportion of trials that provided a definite answer was examined. Completing the trial resulted in reaching a high degree of confidence in the final management decision in 74% of trials. In 35% of trials, results led to discontinuation of the drug which otherwise would have been continued indefinitely. The drug benefit, if present, was evident within first 2 weeks of therapy. We concluded that these results support the feasibility and usefulness of N-of-1 RCT in rheumatology practice.