Background: The Heart Failure Collaboratory (HFC) score integrates types and dosages of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effects of cardioverter-defibrillator (ICD) implantation according to the modified HFC (mHFC) score in 1116 patients with nonischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic HF on Mortality (DANISH). Methods and Results: Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers and mineralocorticoid receptor antagonists (0, no use; 1, < 50% of maximum dosage; 2, ≥ 50% of maximum dosage). The maximum score was 6, corresponding to ≥ 50% of maximum dosage for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with an mHFC score of 3–4, an mHFC score of 1–2 was associated with a higher rate of all-cause death (mHFC = 1–2: adjusted HR 1.67 [95% CI, 1.23–2.28]; mHFC = 3–4, reference; mHFC = 5–6: adjusted HR 1.07 [95% CI, 0.87–1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95% CI, 0.74–1.08]), regardless of mHFC score (mHFC = 1–2: HR 0.98 [95% CI, 0.56–1.71]; mHFC = 3-4: HR 0.89 [95% CI,0.66–1.20]; mHFC = 5–6: HR 0.85 [95% CI, 0.64–1.12]; P_interaction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95% CI, 0.70–1.09]), regardless of mHFC score (P_interaction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40–0.92]); this association was not modified by mHFC score (P_interaction, 0.35). Conclusions: Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with nonischemic HFrEF, regardless of mHFC score.