Background Whether continued follow-up in specialized heart failure (HF) clinics after optimization of guideline-directed therapy improves long-term outcomes in patients with HF with reduced ejection fraction (HFrEF) is unknown. Methods and results 921 medically optimized HFrEF patients enrolled in the NorthStar study were randomly assigned to follow up in a specialized HF clinic or primary care and followed for 10 years using Danish nationwide registries. The primary outcome was a composite of HF hospitalization or cardiovascular death. We further assessed the 5-year adherence to prescribed neurohormonal blockade in 5-year survivors. At enrollment, the median age was 69 years, 24,7% were females, and the median NT-proBNP was 1139 pg/ml. During a median followup time of 4.1 (Q₁-Q₃ 1.5–10.0) years, the primary outcome occurred in 321 patients (69.8%) randomized to follow-up in specialized HF clinics and 325 patients (70.5%) randomized to follow-up in primary care. The rate of the primary outcome, its individual components, and all-cause death did not differ between groups (primary outcome, hazard ratio 0.96 [95% CI, 0.82–1.12]; cardiovascular death, 1.00 [0.81–1.24]; HF hospitalization, 0.97 [0.82–1.14]; all-cause death, 1.00 [0.83–1.20]). In 5-year survivors (N = 660), the 5-year adherence did not differ between groups for angiotensin-converting enzyme inhibitors (p = 0.78), beta-blockers (p = 0.74), or mineralocorticoid receptor antagonists (p = 0.47). Conclusions HFrEF patients on optimal medical therapy did not benefit from continued follow-up in a specialized HF clinic after initial optimization. Development and implementation of new monitoring strategies are needed.