BACKGROUND: The true incidence of, and risk factors for, readmission for treatment failure after nonoperative management of acute diverticulitis remain poorly understood. OBJECTIVE: The purpose of this study was to describe the incidence and risk factors for readmission for treatment failure after nonoperative management of acute diverticulitis using a large national database. DESIGN: This was a retrospective cohort study. SETTINGS: A representative sample of admissions and discharges from hospitals in the United States captured in the National Readmissions Database were included. PATIENTS: Adult patients (age >= 18 y) admitted with a primary diagnostic of colonic diverticulitis between 2010 and 2015 and who were managed nonoperatively and discharged from hospital alive were included. INTERVENTIONS: Study intervention included nonoperative management, consisting of medical therapy with or without percutaneous drainage. MAIN OUTCOME MEASURES: Readmission for treatment failure (defined as a nonelective readmission for diverticulitis within 90 d of discharge), complicated treatment failure (defined as a treatment failure with complicated diverticulitis), and time-to-treatment failure were measured. RESULTS: In total, 201,384 patients were included. The overall incidence of readmission for treatment failure was 6.6%. Treatment failure was significantly higher among patients with an index episode of acute complicated diverticulitis compared with acute uncomplicated diverticulitis (12.5% vs 5.7%; p < 0.001). The median time-to-readmission for treatment failure was 21.0 days (range, 20.4-21.6 d), and 85% of all readmissions occurred within 60 days of discharge. On multiple logistic regression, factors independently associated with readmission for treatment failure were an index admission of complicated diverticulitis (OR = 2.06 (95% CI, 1.97-2.16)), disposition on discharge (against medical advice: OR = 1.92 (95% CI, 1.66-2.20); home health care arrangements: OR = 1.24 (95% CI, 1.16-1.33)), and immunosuppression (OR = 1.42 (95% CI, 1.28-1.57)), among others. Risk factors for a complicated treatment failure were also described, after an index episode of complicated and uncomplicated diverticulitis. LIMITATIONS: The study was limited by residual confounding from missing covariates and its observational study design. CONCLUSIONS: The incidence of readmission for treatment failure after an episode of diverticulitis managed nonoperatively is 6.6%, and an index episode of complicated diverticulitis is the strongest risk factor for treatment failure. See Video Abstract at http://links.lww.com/DCR/B92.