Background: It is unknown whether digital applications can improve guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF)., Methods and Results: Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure trial (CONNECT-HF) included an optional, prospective ancillary study of a mobile health application among patients hospitalized due to HFrEF. Digital users were matched to nonusers from the usual-care group. Coprimary outcomes included change in opportunity-based composite HF quality scores and HF rehospitalization or all-cause mortality. Among 2431 patients offered digital applications across the United States, 1526 (63%) had limited digital access or insufficient data, 425 (17%) were digital users, and 480 (20%) declined use. Digital users were similar in age to those who declined use (mean 58 vs 60 years; P = 0.031). Digital users (n = 368) vs matched nonusers (n = 368) had improved composite HF quality scores (48.0% vs 43.6%; + 4.76% [3.27-6.24]; P = 0.001) and composite clinical outcomes (33.0% vs 39.6%; HR 0.76 [0.59-0.97]; P = 0.027)., Conclusions: Among participants in the CONNECT-HF trial, use of digital applications was modest but was associated with higher HF quality-of-care scores, including use of GDMT and better clinical outcomes. Although cause and effect cannot be determined from this study, the application of technology to guide GDMT use and dosing among patients with HFrEF warrants further investigation., Competing Interests: Disclosures Dr. Rao is supported by an NIH training grant (5T32HL069749-18). Dr. Fonarow reports consulting for Abbott, Amgen, Bayer, Janssen, Medtronic, and Novartis. Dr. Albert reports consulting for Novartis. Dr. Lewis receives research funding from Novartis, Merck, Sanofi AstraZeneca and reports consulting for Novartis, Merck, and Dal-Cor. Dr Butler receives research support from and/or reports consulting for Abbott, Adrenomed, Amgen, Array, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, V-Wave Limited, and Vifor. Dr Allen receives research funding from NIH, PCORI, and AHA, and consulting fees from ACI Clinical, Amgen/Cytokinetics, and Boston Scientific. Dr. Lanfear receives research funding from Amgen, Bayer, the NHLBI, Novartis, and Critical Diagnostics, and reports consulting for Amgen, Abbot Diagnostics, Abiomed, Ortho Diagnostics, Janssen, Hridaya, and the Duke Clinical Research Institute (Akros). Dr. Hernandez receives research funding from American Regent, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck, Novartis, Verily, and reports consulting for AstraZeneca, Bayer, Boehringer-Ingelheim, Boston Scientific, Cytokinetics, Merck, Myokardia and Novartis. Dr DeVore reports research funding through his institution from the American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent, the NHLBI, Novartis and PCORI; he also provides consulting services for Amgen, AstraZeneca, Bayer, CareDx, InnaMed, LivaNova, Mardil Medical, Novartis, Procyrion, scPharmaceuticals, Story Health, and Zoll. He has also received nonfinancial support from Abbott for educational activities. The other authors have no disclosures., (Copyright © 2022. Published by Elsevier Inc.)