Background and Objectives: Therapeutic management of patients with complicated acute diverticulitis remains debatable. The primary objective of this study is to identify predictive factors for the failure of conservative treatment of Hinchey IIa and IIb diverticular abscesses. Materials and Methods: This is a retrospective cohort study that included patients hospitalized from 1 January 2014 to 31 December 2022 at the Emergency Surgery Department of the Cagliari University Hospital (Italy), diagnosed with acute diverticulitis complicated by Hinchey grade IIa and IIb abscesses. The collected variables included the patient's baseline characteristics, clinical variables on hospital admission, abscess characteristics at the contrast-enhanced CT scan, clinical outcomes of the conservative therapy, and follow-up results. Univariable and multivariable logistic regression models were used to identify prognostic factors of conservative treatment failure and success. Results: Two hundred and fifty-two patients diagnosed with acute diverticulitis were identified from the database search, and once the selection criteria were applied, 71 patients were considered eligible. Conservative treatment failed in 25 cases (35.2%). Univariable analysis showed that tobacco smoking was the most significant predictor of failure of conservative treatment (p = 0.007, OR 7.33, 95%CI 1.55; 34.70). Age (p = 0.056, MD 6.96, 95%CI -0.18; 0.99), alcohol drinking (p = 0.071, OR 4.770, 95%CI 0.79; 28.70), platelets level (p = 0.087, MD -32.11, 95%CI -0.93; 0.06), Hinchey stage IIa/IIb (p = 0.081, OR 0.376, 95%CI 0.12; 1.11), the presence of retroperitoneal air bubbles (p = 0.025, OR 13.300, 95%CI 1.61; 291.0), and the presence of extraluminal free air at a distance (p = 0.043, OR 4.480, 95%CI 1.96; 20.91) were the other variables possibly associated with the risk of failure. In the multivariable logistic regression analysis, only tobacco smoking was confirmed to be an independent predictor of conservative treatment failure (p = 0.006; adjusted OR 32.693; 95%CI 2.69; 397.27). Conclusion: The role of tobacco smoking as a predictor of failure of conservative therapy of diverticular abscess scenarios highlights the importance of prevention and the necessity to reduce exposure to modifiable risk factors.