BACKGROUND: Major depressive disorder has been linked to an inability to differentiate between negative emotions. The current study investigates whether emotion differentiation improves when individuals with major depressive disorder are required to report on specific emotions multiple times a day through the experience sampling method (ESM) - a structured self-report diary technique. METHODS: Seventy-nine patients diagnosed with major depressive disorder participated in this study, of whom 55 used ESM for 6 weeks (3 days a week, 10 times a day). Changes from baseline to post assessment in positive and negative emotion differentiation were compared between the participants who did and those who did not use ESM. RESULTS: Engaging in ESM related to an improvement in both positive and negative emotion differentiation, but only the latter reached statistical significance. The relationship between the number of ESM measurements (dose) and emotion differentiation change (response) was not significant. LIMITATIONS: The sample size for the dose-response analysis was relatively small (N = 55). It is unknown whether emotion differentiation improvements generalize beyond the emotions (N = 12) we probed in this study. Other factors could also have contributed to the change (e.g., meetings with the researchers). CONCLUSIONS: The present study suggests that patients with depression using ESM for 3 days a week for 6 weeks can improve their negative emotion differentiation. Future studies should assess after what period of ESM changes in emotion differentiation become apparent, and whether these changes are persistent and relate to actual improvement in depressive symptoms.