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Aims Data on the burden of acute heart failure (AHF) admissions, practice patterns, and outcomes are rare from India and other low- and middle-income countries. We aimed to describe the baseline characteristics, guideline-directed medical therapy (GDMT) prescribing patterns and 90-day mortality rates in patients admitted with AHF in Kerala, India. Methods and results The Cardiology Society of India-Kerala Acute Heart Failure Registry (CSI-KHFR) is an observational registry from 50 hospitals in Kerala, India, with prospective follow-up. Consecutive patients with AHF, who consented to participate, were enrolled. The 2016 European Society of Cardiology criteria were used for the diagnosis of AHF. Kaplan–Meier survival analysis and Cox-proportional hazard models were used for data analysis. The variables in the MAGGIC risk score were used in the multivariable model. A total of 7507 patients with AHF (37% female) participated in the CSI-KHFR. The mean age was 64.3 (12.9) years. More than two-third had reduced ejection fraction (EF) (67.5%). Nearly one-fourth (28%) of patients with heart failure (HF) with reduced EF received GDMT. Overall, in-hospital and 90-day mortality rates were 7% and 11.6%, respectively. Prescriptions of different components of GDMT were independently associated with 90-day mortality. Conclusion The CSI-KHFR recorded an in-hospital and 90-day mortality of 7% and 11.6%, respectively. Only one of four patients received GDMT. AHF mortality was independently associated with GDMT initiation. Quality improvement initiatives that focus on increasing GDMT prescription may improve the survival of HF patients in India.