Nocturia is a highly prevalent and under-considered condition and impacts the quality of life for many individuals. The long-term impact of nocturnal voiding on mortality, especially mortality from cardiovascular disease, remains unknown. The current study aimed to evaluate the relationship of nocturnal voiding episodes with cardiovascular and all-cause mortality among adults in the United States. This is a prospective cohort study of a nationally representative sample of 13,862 U.S. adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey III (1988-1994). Nighttime urination frequency was reported during an in-house interview. All-cause and cause-specific mortality were ascertained by linking to National Death Index mortality data through December 31, 2019. The associations of nocturia with cardiovascular and all-cause mortality were estimated using weighted Cox proportional hazards regression models. Throughout a median follow-up of 26.7 years, 5,029 deaths were reported, comprising 1,720 deaths from cardiovascular disease. In the fully adjusted model, participants who reported once, twice, and three or more times nocturnal voiding episodes have a higher risk of cardiovascular mortality (HR1, 1.22 [95% CI, 0.997-1.49], HR2, 1.47 [95% CI, 1.13-1.91], and HR ≥ 3, 1.96 [95% CI, 1.52-2.53]) as well as all-cause mortality (HR1, 1.12 [95% CI, 0.90-1.39], HR2, 1.54 [95% CI, 1.23-1.93], and HR ≥ 3, 2.48 [95% CI, 1.81-3.40]), compared to those without nocturia, and heart disease-specific mortality (HR1, 1.33 [95% CI, 1.08-1.64], HR2, 1.62 [95% CI, 1.25-2.10], and HR≥3, 2.07 [95% CI, 1.61-2.67]). Nevertheless, there was no significant relationship between the number of nocturia episode changes and stroke-specific mortality. Nocturia was associated with a significantly augmented risk of overall and heart disease-specific mortality in a dosage-dependent manner. Early recognition and taking precautions may benefit individuals with nocturia by promoting quality of life and cardiac health.