BACKGROUND Recent studies have suggested a high prevalence of cardiac amyloidosis (CAm) in heart failure (HF) patients. CAm might be underdiagnosed owing to low clinical suspicion. METHODS AND RESULTS We performed retrospective analysis of 259 patients with HF and ejection fraction (EF) ≥50% referred for endomyocardial biopsy. Seventy-three (28%) had CAm. Multivariable independent predictors of CAm were identified. Over a mean follow-up of 2.6 ± 3.3 years, CAm patients had worse survival than those without (1.5 y vs 6.3 y; log rank P < .0001). CONCLUSIONS Clinicians should be suspicious of CAm in patients with EF 50%-75%, >50 years of age, BMI <30 kg/m2, peripheral neuropathy, Sokolow-Lyon index ≤15 mm, and septal wall thickness ≥1.4 cm.