AimsTo investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline‐directed medical HF therapy (GDMT) and consequent outcomes.Methods and resultsAmong patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009–2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1–4.0 vs. 1.4–1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1–44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin–angiotensin system inhibitors/angiotensin receptor–neprilysin inhibitors or beta‐blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.ConclusionsFollowing a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re‐/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re‐/initiation of GDMT following a HF hospitalization.