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Abstract Background Obesity is a well-defined risk factor for heart failure with preserved ejection fraction (HFpEF), but it is associated with a better prognosis in patients with diagnosed HFpEF. The paradoxically poor prognosis in nonobese patients with HFpEF may be driven by a subset of high-risk patients, which suggests that the nonobese HFpEF subpopulation is heterogeneous. Methods Latent class analysis (LCA) was adopted to identify the potential subgroups of 623 nonobese patients enrolled in the TOPCAT trial. The baseline characteristics of the identified nonobese subgroups were compared with each other and with the obese patients. The risks of all-cause, cardiovascular, and noncardiovascular mortality, and an HF composite outcome were also compared. Results Two subgroups of nonobese patients with HFpEF (the physiological non-obesity and the pathological non-obesity) were identified. The obese patients were younger than both nonobese subgroups. The clinical profile of patients with pathological non-obesity was poorer than that of patients with physiological non-obesity. They had more comorbidities, more severe HF, poorer quality of life, and lower levels of physical activity. Patients with pathological non-obesity showed low serum hemoglobin and albumin levels. After 2 years of follow-up, more patients in the pathological group lost ≥ 10% of body weight compared with those in the physiological group (11.34% vs. 4.19%, P = 0.009). The prognostic implications of the two subgroups were opposite. Compared to patients with obesity, patients with physiological non-obesity had a 47% decrease in the risk of HF composite outcome (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40–0.70, P