Abstract Background Poor drug adherence in heart failure (HF) is associated with increased morbidity and mortality. Aims We aimed to investigate compliance to European guidelines for treatment of HF in Norway by measuring initiation and persistence of inhibitors of the renin-angiotensin system (RASi), β-blockers (BB) and mineralocorticoid receptor antagonists (MRA). Methods We included all patients ≥18 years with a first hospital contact for HF registered in the Norwegian Patient Registry (NPR) between 2014–2020. Patients >80 years of age and patients that deceased within the first 30 days were excluded. The study population was linked to the Norwegian Prescription Database for longitudinal data on drug prescriptions. Dual HF therapy was defined as taking at least two recommended HF drug classes, triple HF therapy was defined as taking all three drug classes. To estimate initiation, we counted the days from index HF to the first HF prescription, dual HF therapy and triple HF therapy within the first 365 days. We repeated the analysis for drug-naive patients, as some patients receive HF drugs for other indications or based on a tentative HF diagnosis. Patients were considered persistent if they did not experience any treatment break of more than 30 days. We allowed for stockpiling up to a maximum of 60 days, except for when the dose changed or if patients switched medication within the same drug class. Initiation and persistence were calculated by the Kaplan-Meier method, followed to death or December 2020. Results Out of 54,899 patients, 75%, 69% and 21% initiated BB, RASi and MRA, respectively (Figure 1). 13% of the population did not receive any of the three drug groups. Dual HF therapy was prescribed to 61% of the patients and triple HF therapy to 16%. In drug-naive patients, a lower proportion received any HF-drug within the first year (BB, 61%; RASi, 55%; and MRA, 19%), however, a higher proportion was collected within the first 30 days (BB, 48%; RASi, 46%; and MRA, 11%). Among the patients initiating therapy, 72% were persistent on BB, 71% on RASi and 48% on MRA throughout the first year with prominent declines in persistence around 3 and 6 months after initiation (Figure 2). Two years after initiation, the proportions of patients on BB, RASi and MRA decreased to 58%, 57% and 31%, respectively. The 5-year persistence was 38%, 37% and 15%, respectively. Conclusion This study found poor treatment compliance to HF medications in a real-world population of HF patients with only 61% of patients initiating dual pharmacotherapy and only 16% received all three dug classes. Nearly half of the patients discontinued RASi and BB within 2 years. The results suggest that systematic efforts should be done to increase the proportion of patients on guideline recommended therapies. These efforts should be focused on early initiation of multiple drug therapies as well as to maintain patients on treatment over time. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Novartis Norway AS and The Norwegian Research Council