Aims: To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes. Methods and Results: Among 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 vs. without a HF hospitalization. Of 14,737 patients, 6,893 (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, respectively), although the percentage 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-systeminhibitors/angiotensin-receptor-neprilysin-inhibitors or betablockers 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. Conclusion: Following 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 guidelines recommendation for an early re-/initiation of GDMT following a HF hospitalization.