BACKGROUND: Data are limited on the natural history and symptom patterns of cyclic vomiting syndrome (CVS), a disorder of gut-brain interaction characterized by recurrent stereotypical vomiting, retching, and nausea episodes. METHODS: A 6-month, observational, remote study prospectively assessed symptom patterns in adults with CVS using an electronic daily diary. Patients recorded their disease experience, including CVS symptoms and associated severity, in the daily diary. The study defined a CVS episode start as the first day of 5 or more vomiting and/or retching (V + R) events. Episode end was defined as the first day of ≥ 7 (prespecified main analysis) or ≥ 4 (sensitivity analysis) days without any diary V + R events. KEY RESULTS: Eighty-eight of 93 (94.6%) enrolled patients (62 female; mean age, 37.7 years) had daily diary data recorded during the study; 61 (69.3%) patients had at least one episode. In the prespecified main analysis, 191 episodes (median, 0.6 per 30 diary days) were reported (median duration, 3.0 days); 17.8% of the episodes lasted > 10 days. In the sensitivity analysis, 248 episodes (median, 0.7 per 30 diary days) were reported (median duration, 2.0 days). Thirteen of 88 (14.8%) patients with diary data had interepisodic V + R (reported V + R events without meeting the threshold for study-defined episode). Other CVS-related (non-V + R) symptoms (most frequently nausea, abdominal pain, and sweating) were reported more frequently during the episode versus the interepisodic period. CONCLUSIONS AND INFERENCES: This prospective longitudinal study shows marked heterogeneity of CVS episodes and highlights the need to better define and characterize episodes in these patients.