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To evaluate and compare the effects of cardiovascular risk factors (hypertension, smoking, diabetes) and noise exposure (occupational, recreational, firearm) on frequency-specific audiometric thresholds among US adults while assessing synergistic interactions between these exposures.National cross-sectional survey.United States adults aged 20 to 69 years who participated in the 1999 to 2002 National Health and Nutrition Examination Survey (N = 3,527).Air-conduction thresholds at 0.5 to 8 kHz (dB) in the poorer-hearing ear. Multivariate models adjusted for age, sex, race/ethnicity, and educational level.Exposure to firearm noise was significantly associated with high-frequency (4-8 kHz) hearing loss (HL), whereas smoking and diabetes were associated with significantly increased hearing thresholds across the frequency range (0.5-8 kHz). A significant interaction was observed between exposure to firearm noise and heavy smoking such that firearm noise was associated with a mean 8-dB hearing loss in heavy smokers compared with a mean 2-dB hearing loss in nonsmokers at 8 kHz. We also observed significant interactions between firearm noise exposure and diabetes.Noise exposure was associated with high-frequency HL, whereas cardiovascular risk generated by smoking and diabetes was associated with both high- and low-frequency HL. The frequency-specific effects of these exposures may offer insight into mechanisms of cochlear damage. We demonstrated an interaction between cardiovascular risk and noise exposures, possibly as a result of cochlear vulnerability due to microvascular insufficiency. Such significant interactions provide proof of principle that certain preexisting medical conditions can potentiate the effect of noise exposure on hearing. Data-based stratification of risk should guide our counseling of patients regarding HL.