The aim of this meta-analysis was to assess the effectiveness of acetazolamide as an add-on diuretic therapy in patients with heart failure. This meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. A systematic literature search was independently performed by two authors using MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews to identify relevant studies assessing the use of acetazolamide in patients with heart failure. The search keywords included "acetazolamide" and "heart failure". The outcomes assessed in this meta-analysis included natriuresis (mmol/L), diuresis (Liters) and decongestion (absence of signs of volume overload) by 72 hours. Other outcomes assessed in this meta-analysis included hospitalization due to heart failure and all-cause mortality. A total of three studies included a total of 569 heart failure patients. The number of patients achieved decongestion was significantly higher in patients receiving acetazolamide compared to the patients randomized in the control group (RR: 1.34, 95% CI: 1.06-1.67). Compared to patients in the control group, mean natriuresis was significantly higher in acetazolamide patients (MD: 74.91, 95% CI: 39.85-109.97). Diuresis was significantly higher in patients receiving acetazolamide compared to the control group (MD: 0.44, 95% CI: 0.16-0.72). No significant difference was found between the two groups in terms of all-cause mortality and hospitalization due to heart failure. In conclusion, our meta-analysis suggests that acetazolamide may have beneficial impacts on heart failure patients by increasing the number of successful decongestions. Additionally, patients who were treated with acetazolamide had significantly higher natriuresis and diuresis compared to patients in the control group.