Background <p>Loop diuretics relieve congestion in chronic heart failure (CHF). We systematically reviewed randomised clinical trials (RCTs) evaluating their effects.</p> Methods <p>A systematic search was conducted across major databases. We included RCTs that compared a loop diuretic to another loop diuretic, placebo, or “no intervention”. The primary outcome was all-cause mortality, and secondary outcomes were all-cause hospitalisation, serious adverse events (SAEs), and change in body weight (kg).</p> Results <p>This review included 23 RCTs that enrolled 4,902 patients. Treatment with alternative loop diuretics (torsemide, azosemide and piretanide) compared with furosemide did not reduce all-cause mortality (risk ratio 1.00, 95% CI 0.89, 1.12); <i>I</i>^<i>2</i> = 0%; <i>p</i> = 0.95), nor did it reduce all-cause hospitalisations (risk ratio 0.99, 95% CI 0.84, 1.17); <i>I</i>^<i>2</i> = 53,46%, <i>p</i> = 0.92). In a pooled analysis of alternative loop diuretics (including torsemide and piretanide) the risk of SAEs was higher compared to furosemide (risk ratio 1.32, 95% CI 1.03, 1.68); <i>I</i>^<i>2</i> = 0%), although this finding was based on a limited number of trials with inconsistent definitions and should therefore be interpreted cautiously. The pooled meta-analysis of change in body weight did not show a difference between loop diuretics (mean difference 0.00&#xa0;kg, 95% CI -1.19, 1.20; <i>I</i>^<i>2</i> = 92.43), indicating substantial heterogeneity. Azosemide resulted in a significant weight loss reduction compared to furosemide (mean difference − 1.00&#xa0;kg, 95% CI -1.42, -0.58) based on a single small study.</p> Conclusions <p>The choice of loop diuretic did not seem to influence the risk of mortality. In a pooled analysis of torsemide and piretanide, the risk of SAEs was higher when compared to furosemide, but the certainty of this finding is limited. Azosemide was associated with weight loss compared to furosemide in one small trial.</p>