BACKGROUND: Although acute diverticulitis and its recurrence are well studied, little is known about the period after these attacks have passed. Many patients appear to be affected by persistent symptoms that impair quality of life. The few published studies on this topic are mostly limited by the lack of CT confirmation of the acute diverticulitis diagnosis, low numbers of patients, or cross-sectional design. OBJECTIVE: This study longitudinally evaluated quality of life and symptoms after antibiotic or observational treatment of uncomplicated acute diverticulitis. DESIGN: This was an observational study of randomized clinical trial data. SETTINGS: This study was conducted at a single tertiary care center. PATIENTS: Patients with CT-proven, primary, left-sided, uncomplicated acute diverticulitis were randomly assigned to observational or antibiotic treatment. MAIN OUTCOME MEASURES: Quality of life was assessed using questionnaires (EuroQol 5D, Short Form-36, and Gastrointestinal Quality of Life Index) at baseline and 3, 6, 12, and 24 months after random assignment. Patients were considered to have persistent symptoms when specific quality-of-life scores at the 12- and 24-month follow-ups were among the lowest 16% of scores measured in a healthy reference group. RESULTS: A total of 528 patients were included. No difference was detected between the observational and antibiotic groups in any quality-of-life score during follow-up. Overall, 32.2% to 38.2% of patients had persistent symptoms after 1 or 2 years, depending on which questionnaire (sub)score was assessed. Risk factors for persistent symptoms based on to the Gastrointestinal Quality of Life index GI symptoms score included a mean pain score ≥3.75 (OR = 2.77 (95% CI, 1.60-4.80)) during the first 10 days of disease and prolonged (≥28 d) time to recovery (OR = 2.25 (95% CI, 1.31-3.88)). Flatulence, rumblings, bloating, fullness, and many stools were the top 5 complaints at the 12- and 24-month follow-ups. LIMITATIONS: The study was limited by possible selection bias of patients included in a randomized controlled trial. CONCLUSIONS: More than one third of patients experience persistent symptoms after an episode of acute uncomplicated diverticulitis. Long-term quality of life is comparable after initial antibiotic or observational treatment. See Video Abstract at http://links.lww.com/DCR/A916.