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Background: This study aimed to explore the feasibility of guiding the application of metoprolol succinate in patients with moderate to severe heart failure (HF) through monitoring plasma brain natriuretic peptide (BNP) levels., Methods: A total of 195 patients with moderate to severe HF (NYHA Functional Class III to IV) were selected and randomized into two groups: an observation group and a BNP group. The groups were established to observe the clinical conditions and establish plasma BNP levels to guide the application of metoprolol succinate. The average start-up of metoprolol succinate and average dose of metoprolol succinate after one month, as well as the recurrence rate and mortality of HF during hospital stay were compared between the two groups., Results: Start-up of metoprolol succinate was shorter in the BNP group than in the observation group [(5.89 ± 1.76) d vs. (7.03 ± 2.08) d, p < 0.01], but no significant differences in recurrence rate (26.60% vs. 23.91%, p > 0.05) and mortality (6.38% vs. 5.43%, p > 0.05) of HF were observed between the two groups. The average dose of metoprolol succinate after one month was higher in the BNP group compared with that of the observation group [(47.65 ± 13.09) mg/d vs. (35.08 ± 11.08) mg/d, p < 0.01]., Conclusions: Although monitoring plasma BNP might have limited the clinical impact on the change of left ventricular ejection fraction, recurrence of HF or mortality within 1 month, it could safely facilitate early use and up-titration of the metoprolol succinate in patients with moderate to severe HF., Key Words: BNP; Heart failure; β receptor blocker.