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Background: Sexual activity appears to have protective effects on overall and cardiovascular health., Aim: We hypothesized that decreased sexual frequency would be an early predictor of all-cause mortality in young and middle-aged patients (20 to 59 years old) with hypertension., Methods: A total of 4565 patients with hypertension (55.6% men; mean [SD] age 40.60 [10.81] years) who had completed a sexual behavior questionnaire were enrolled from the National Health and Nutrition Examination Survey of 2005 to 2014. Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate the relationship between sexual frequency and all-cause mortality., Outcomes: The outcome measure for this study is the relationship between sexual frequency and all-cause mortality in young and middle-aged patients with hypertension., Results: During the 68-month median follow-up period, 109 (2.39%) patients died from any cause. After full adjustment for potential confounders, sexual frequency was an independent predictive factor for all-cause mortality in young and middle-aged patients with hypertension. A marital status difference was identified in the subgroup analysis: among patients with a sexual frequency of <12 times/year, only married patients had higher risks of all-cause mortality than the 12-51 times/year group (HR, 0.476, 95% CI, 0.235-0.963, P < .05) and > 51 (HR, 0.452, 95% CI, 0.213-0.961, P < .05) times/year groups. The association of sexual frequency and all-cause mortality was nonlinear., Clinical Implications: Increased frequency of sexual activity may have protective effects on overall health and quality of life in patients with hypertension., Strengths and Limitations: To our knowledge this is the first observational investigation performed to evaluate the correlation between sexual frequency and all-cause mortality in patients with hypertension. A limitation of the study is that the participants in our analysis were between the ages of 20 and 59 years, and this patient sample may not reflect possible outcomes for patients of other age groups., Conclusion: The association between lower frequency of sexual intercourse and greater all-cause mortality was significant in young and middle-aged patients with hypertension in the United States., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)