Abstract Introduction Persistent congestion in acute congestive heart failure despite conventional treatments highlights the need for innovative therapeutic approaches. Evaluating acetazolamide as adjunctive therapy for reducing volume overload is significant. Our meta-analysis examines randomized clinical trials to assess acetazolamide's efficacy in improving fluid management in acute congestive heart failure. Methods We systematically searched Embase, PubMed, and the Cochrane Library in January 2024 for randomized controlled trials comparing the addition of acetazolamide to diuretic therapy versus standard diuretic therapy in patients with acute congestive heart failure. Article selection was conducted independently by two authors. Statistical analyses, including the weighted mean differences (MD) and assessment of heterogeneity using the I² statistic, were performed using R software version 5.4.1. Results Three studies comprising 596 patients were included. Of these, 297 (50%) received acetazolamide as adjunctive diuretic therapy, while 299 (50%) received standard diuretic therapy with a loop diuretic. Among participants, 385 (65%) were male, with a mean age of 72.76 years (±11.13). Acetazolamide adjunctive therapy led to an increase in natriuresis at day 2, expressed in milimoles (mmol), (MD 80.30; 95% CI [45.10-115.51]; p<0.00001; I2=29%), and a trend towards higher natriuresis volume, expressed in liters (L), at day 2 (MD 0.56; 95% CI [-0.37-1.48]; p=0.24; I2=87%), although the latter lacked statistical significance. Conclusions Our findings suggest that acetazolamide adjunctive therapy may have potential benefits in improving fluid management and possibly enhancing clinical outcomes in patients with acute congestive heart failure. Further research is warranted to validate these findings and explore the long-term effects of acetazolamide therapy.