Objective: To estimate a minimal clinically important difference (MCID) on the adult ADHD Quality of Life (AAQoL) scale. Method: The MCID was determined from data from short-term (N = 537) and long-term (N = 440), placebo-controlled atomoxetine trials in adults with ADHD. For the anchor-based approach, change in clinician-rated Clinical Global Impressions–ADHD–Severity (CGI-ADHD-S) scores was used to derive MCID. For the distribution-based approach, baseline-to-endpoint mean (SD) changes in AAQoL scores corresponding to 0.5 SD were computed. Results: The MCID was similar (approximately 8-point difference) between the short-term and the long-term treatment groups when either the anchor-based or distribution-based approach was used. Conclusion: These results suggest that approximately 8 points in the change from baseline on the AAQoL is a MCID.