Peptic ulcers with adherent clots are associated with a high-risk of rebleeding and mortality. However, the optimal management of bleeding ulcers with adherent clots remains unclear. We conducted this systematic review and meta-analysis to compare endoscopic therapy and conservative therapy to manage bleeding ulcers with adherent clots. We systematically searched PubMed, Embase, and Web of Science databases through October 2022 to include all studies comparing the endoscopic and conservative therapeutic approaches for bleeding ulcers with adherent clots. Our primary outcome was rebleeding (overall and 30-day). The secondary outcomes were mortality (overall and 30-day), need for surgery, and length of hospital stay (LOS). The random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding confidence intervals (CI) for proportional and continuous variables, respectively. Eleven studies (9 RCTs) with 833 patients (431 received endoscopic therapy vs. 402 received conservative therapy) were included. Overall, endoscopic therapy was associated with lower overall rebleeding (OR 0.41, 95% CI 0.22-0.79, P = 0.007), 30-day rebleeding (OR 0.43, 95% CI 0.21-0.89, P = 0.002), overall mortality (OR 0.47, 95% CI 0.23-0.95, P = 0.04), 30-day mortality (OR 0.43, 95% CI 0.21-0.89, P = 0.002), need for surgery (OR 0.44, 95% CI 0.21-0.95, P = 0.04), and LOS (MD - 3.17 days, 95% CI - 4.14, - 2.19, P < 0.00001). However, subgroup analysis of randomized controlled trials (RCTs) showed no significant difference in overall mortality (OR 0.78, 95% CI 0.24-2.52, P = 0.68) between the two strategies, with numerically lower but statistically non-significant rates of overall rebleeding (7.2% vs. 18.5%, respectively; OR 0.42, 95% CI 0.17-1.05, P = 0.06), statistically lower rate of need for surgery (OR 0.28, 95% CI 0.08-0.96, P = 0.04) with endoscopic therapy compared to conservative therapy. Our meta-analysis demonstrates that endoscopic therapy was overall associated with lower rates of rebleeding (overall and 30-day), mortality (overall and 30-day), need for surgery, and LOS, compared to conservative therapy for the management of bleeding ulcers with adherent clots. However, subgroup analysis of RCTs showed that endoscopic therapy was associated with numerically lower but statistically non-significant rates of overall rebleeding and a statistically lower rate of need for surgery compared to conservative therapy with similar overall mortality rates. Combined treatment with thermal therapy and injection therapy was the most effective treatment modality in reducing rebleeding risk. Further large-scale RCTs are needed to validate our findings.