Non-operative treatment is the mainstay of colonic diverticulitis, but some patients require surgery due to non-operative treatment failure. This study aims to identify risk factors for the failure of non-operative treatment of colonic diverticulitis. From January 2011 to December 2020, we retrospectively reviewed 2362 patients with non-operative treatment for first-attack acute diverticulitis. Patients were categorized into non-operative treatment success or failure groups. Clinical characteristics and serum inflammatory markers were analyzed by multivariable logistic regression to determine risk factors for non-operative treatment failure of colonic diverticulitis. Overall, 2.2% (n = 50) of patients underwent delayed surgery within 30 days (median 4.0 3.0; 8.0) due to non-operative treatment failure. Multivariable logistic regression identified that platelet to lymphocyte ratio (odds ratio OR, 4.2; 95% confidence interval CI, 0.05-0.13; p < 0.001), diabetes mellitus (OR, 2.2; 95% CI, 0.01-0.09; p = 0.025), left-sided colonic diverticulitis (OR, 4.1; 95% CI, 0.04-0.13; p < 0.001), and modified Hinchey classification (OR, 6.2; 95% CI, 0.09-0.17; p < 0.001) were risk factors for non-operative treatment failure. Platelet to lymphocyte ratio (PLR) is a potential risk factor for the non-operative treatment failure of acute first-attack colonic diverticulitis. Therefore, patients with higher PLR during non-operative treatment should be monitored with special caution.