Introduction There are limited data on ivabradine therapy in black patients and none in African Americans. We performed an open-label, prospective study at two centers in the United States. African American patients with heart failure (HF) ( N = 30), left ventricular ejection fraction ≤ 35%, and in sinus rhythm with resting heart rate (HR) ≥ 70 bpm received ivabradine 2.5–7.5 mg twice daily for 57 days. Methods The primary endpoint was change in HR from baseline to day 57, compared with the −5 bpm change observed in the absence of ivabradine in the placebo group of the SHIFT study. The safety endpoint was treatment-emergent adverse events (TEAEs). Exploratory endpoints were change from baseline to day 57 in 6-minute walk test (6MWT) distance, HR difference during a 6MWT (i.e. HR at minute 6 − resting HR), and physical activity counts. Results At day 57, the estimated least squares mean change from baseline in HR was −9.5 bpm (95% CI −13.0, −6.0). The estimated mean treatment difference with ivabradine versus a presumed −5 bpm change from baseline HR, as seen in the placebo group of the SHIFT study, was −4.5 bpm (95% CI −8.0, −1.0; p = 0.013). The mean (SE) changes in 6MWT distance and HR difference during the 6MWT were 16.3 (10.8) meters and 2.3 (3.7) bpm, respectively. Ivabradine therapy did not result in greater physical activity. TEAEs were reported in 11 (36.7%) patients. Conclusion These data support ivabradine use in African American patients with HF with reduced ejection fraction who meet typical treatment criteria. Trial Registration ClinicalTrials.gov identifier, NCT03456856 Electronic supplementary material The online version of this article (10.1007/s40119-020-00196-1) contains supplementary material, which is available to authorized users.