OBJECTIVE: To examine pain treatment preferences before and after participation in an N-of-1 trial. STUDY DESIGN AND SETTING: In this observational study nested within a randomized trial, we examined chronic pain patients preferences before and after treatment in relation to N-of-1 trial results; assessed the influence of different schemes for defining comparative superiority on potential conclusions; and generated classification trees illustrating the relationship between pre-treatment preferences, N-of-1 trial results, and post-treatment preferences. RESULTS: Treatment preferences differed pre- and post-trial for 40% of participants. The proportion of patients whose N-of-1 trials demonstrated superiority of one treatment regimen over the other varied depending on how superiority was defined and ranged from 24% (using criteria that required statistically significant differences between regimens) to 62% (when relying only on differences in point estimates). Regardless of criteria for declaring treatment superiority, nearly three-fourths of patients with equivocal N-of-1 trial results nevertheless expressed definite preferences post-trial. CONCLUSION: A large segment of patients undergoing N-of-1 trials for chronic pain altered their treatment preferences. However, the direction of preference change did not necessarily correspond to the N-of-1 results. More research is needed to understand how patients use N-of-1 trial results, why preferences are sticky even in the face of personalized data, and how patients and clinicians might be educated to use N-of-1 trial results more informatively.