ABSTRACT Aims Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR) has not been described. Methods and results The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge‐to‐edge repair (TEER) with the MitraClipTM plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate‐to‐severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7–4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4‐year rates of all‐cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02–1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all‐cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (pinteraction = 0.19 and 0.35 for death and HFH, respectively). Conclusion Low baseline serum albumin levels were independently associated with reduced 4‐year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level. Patients with heart failure with moderate‐severe/severe mitral regurgitation stratified by serum albumin level. CI, confidence interval; GDMT, guideline‐directed medical therapy; HFH, heart failure hospitalization; HR, hazard ratio; TEER, transcatheter edge‐to‐edge repair.