Background Pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality. In the last two decades, significant advances have been made in management of World Health Organization (WHO) group 1 PH. However, there are no approved targeted pharmacotherapies for PH secondary to left-sided heart diseases or chronic hypoxic lung diseases which are thought to account for more than 70–80% of the disease burden. No recent investigation has analyzed and compared the mortality burden related to WHO group 1 PH with the mortality burden with WHO groups 2–5 PH at the national level in the United States (US). We hypothesize that WHO group 1 PH-related mortality has improved over the last two decades in comparison to WHO groups 2–5 PH. Methods In this study, we used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) the underlying cause of death database to study age-standardized mortality rates related to PH in the US from 2003 to 2020. Results A total of 126,526 deaths were recorded from PH in the US between 2003 and 2020. Across the study period, PH-related ASMR increased from 17.81 per million population in 2003 to 23.89 in 2020 with a percentage change (PC) of +34%. However, there are contrasting mortality trends in WHO group 1 PH when compared to WHO groups 2–5 PH. Data demonstrated a decline in mortality from group 1 PH regardless of gender. In contrast, an increase in mortality from WHO groups 2–5 PH was observed, accounting for the major proportion of the overall PH mortality burden in recent years. Conclusions PH-related mortality continues to an increase primarily due to increase in mortality attributed to WHO groups 2–5 PH. These findings have notable public health implications. Screening and risk assessment tools for secondary PH, risk factor modification, and novel management strategies are vital to improve outcomes.

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