Clinical trials for acute heart failure syndromes (AHFS) have traditionally enrolled patients well after emergency department (ED) presentation. We hypothesized a large proportion of patients would undergo changes in clinical profiles during the first 24 h of hospitalization, and these changes would be associated with adverse events. We evaluated a prospective cohort of patients with clinical data available at ED presentation and 12–24 h after ED treatment for AHFS. Patients were categorized into distinct clinical profiles at these time points based on (1) systolic blood pressure: a—hypertensive (>160 mmHg); b—normotensive (100–159 mmHg); or c—hypotensive (<100 mmHg); (2) moderate-to-severe renal dysfunction (GFR ≤ 60 ml/min/1.73 m²); and (3) presence of troponin positivity. A composite outcome of 30-day cardiovascular events was determined by phone follow-up. In the 370 patients still hospitalized with data available at the 12–24 h time point, 196 (53.0%) had changed their clinical profiles, with 117 (59.7%) improving and 79 (40.3%) worsening. The composite 30-day event rate was 16.9%. Patients whose clinical profile started and stayed abnormal had a significantly greater proportion of events than those who started and stayed normal (26.1% vs. 11.3%; P = 0.03). Patients with abnormal clinical profiles at presentation that remain abnormal throughout the first 12–24 h of hospitalization are at increased risk of 30-day adverse events. Future clinical trials may need to consider targeting these patients, as they may be the most likely to benefit from experimental therapy.