Objective: Heart failure (HF) remains a major global health challenge. We evaluated ten-year trends in clinical profiles, diagnostic/therapeutic management, and outcomes in patients hospitalized for de novo acute heart failure (AHF). Methods: We compared two multicenter cohorts of patients admitted to Internal Medicine departments in Spain for a first episode of HF (excluding acutely decompensated chronic HF): a retrospective cohort (CH-2005; n = 600) and a prospective cohort (CH-2015; n = 180). We assessed clinical characteristics, adherence to guideline-recommended diagnostic testing, discharge treatment, and 12-month outcomes (HF readmissions and all-cause mortality). Results: The patients in CH-2015 showed a markedly higher comorbidity burden (Charlson Comorbidity Index > 2: 90.0% vs. 12.8%, p < 0.001) and higher chronic kidney disease prevalence (17.8% vs. 11.8%, p = 0.01), while mean age was similar (75.0 vs. 73.6 years, p = 0.16). Diagnostic adherence improved with higher echocardiography use (92.2% vs. 66.5%, p < 0.001). Discharge beta-blocker prescriptions increased (50.6% vs. 31.3%, p < 0.001). HF readmissions were higher in CH-2015 at 1 month (35.6% vs. 7.3%, p < 0.001) and 12 months (49.4% vs. 21.2%, p < 0.001). One-year mortality was higher in CH-2015 (22.5% vs. 16.3%, p = 0.07). In the multivariable analyses, the between-cohort difference in mortality was not significant, whereas the higher readmission risk in CH-2015 persisted. Conclusions: Over a decade, de novo AHF admissions shifted toward a more complex, multimorbid phenotype. Despite improved diagnostic testing and small advances in evidence-based therapy, the readmission burden increased, highlighting the need for integrated, post-discharge management strategies in older multimorbid populations.