ABSTRACTAimsTo investigate the use of guideline‐directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m²) versus non‐obese patients with heart failure (HF) with reduced ejection fraction (HFrEF).Methods and resultsPatients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non‐obese patients, use of treatments was 91% versus 86% for renin–angiotensin system inhibitors (RASi)/angiotensin receptor–neprilysin inhibitors (ARNi), 94% versus 91% for beta‐blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta‐blockers being independently associated with lower risk of all‐cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non‐obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non‐obese patients, whereas beta‐blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity.ConclusionObese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta‐blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non‐obese patients when considering competing risk.