Serelaxin is recombinant human relaxin-2 which is a naturally occurring peptide that regulates maternal adaptations to pregnancy. It increases arterial compliance, cardiac output, and renal blood flow and these effects may be potentially relevant to the treatment of acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo. RELAX-AHF was a prospective, randomized, double blind, placebocontrolled, parallel-group trial comparing serelaxin with placebo in patients admitted to hospital for acute heart failure. It enrolled patients at 96 sites in 11 countries. Patients were eligible for enrolment if they presented within the previous 16 hours with dyspnoea at rest or  with minimum exertion, pulmonary congestion on chest radiograph, and BNP 350 ng/L or higher or NT-proBNP 1400 ng/L or higher, as well as mild to moderate renal dysfunction, SBP greater than 125 mmHg, and treatment with at least 40 mg intravenous furosemide or its equivalent before screening. The exclusion criteria included treatment with other intravenous heart failure drugs (except intravenous nitrate ≤ 0.1 mg/kg per hour in patients with SBP at screening of >150 mmHg) or mechanical support within 2 hours before screening, signs of active infection, known significant pulmonary or valvular disease, acute heart failure due to significant arrhythmias, acute coronary syndrome diagnosed within 45 days, or a troponin concentration three times or more higher than the level diagnostic of myocardial infarction. It randomized 1161 patients to one of the two treatment groups (serelaxin 30 μg/kg per day or placebo). The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 hours, both analyzed by intention to treat. Serelaxin improved the VAS AUC primary  yspnoea endpoint by 19% (448 mm × h, 95% CI 120–775; p=0.007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale;  p=0.70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure.  Serelaxin treatment was associated with significant reductions in other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0.63, 95% CI 0.42–0.93; p=0.019).