IntroductionFibrinolytic agents (FA) activate the fibrinolytic system, converting plasminogen into plasmin to break down fibrin. Their use for irrigation of abdominal abscesses is debated, and this meta‐analysis evaluates their efficacy.MethodsWe searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing FA and saline in percutaneous drainage of abdominal abscesses. Outcomes included length of hospitalization, duration of drainage, and drainage volume. We pooled mean differences (MD) and 95% confidence intervals (CI) using a random‐effects model. We also performed a trial sequential analysis (TSA).ResultsWe included six RCTs encompassing 299 patients. In the overall analysis, FA increased drainage volume (MD 104.25 mL; 95% CI 35.72–172.77 mL; p = 0.003; I2 = 0%). In children, saline reduced hospitalization duration (MD −1.26 days; 95% CI −1.98 to −0.55 days; p = 0.0006; I2 = 0%), whereas FA increased drainage volume (MD 84.66 mL; 95% CI 5.77–153.54 mL; p = 0.04; I2 = 0%). In adults, FA significantly reduced hospitalization duration (MD −11.12 days; 95% CI −15.16 to −7.08 days; p < 0.00001; I2 = 0%) and duration of drainage (MD −6.53 days; 95% CI −9.25 to −3.81 days; p < 0.00001; I2 = 0%) while increasing drainage volume (MD 164.47 mL; 95% CI 26.16–302.78 mL; p = 0.02; I2 = 0%). On TSA, the required information size was achieved only for the adult subgroup's hospitalization and drainage duration.ConclusionIn adults, FA reduce hospitalization and drainage duration and increase drainage volume. In children, saline seems more effective in reducing hospitalization duration, while FA increase drainage volume. These findings underscore the need for age‐specific treatments and further research, especially in the pediatric population.