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Purpose: Insufficient evidence currently exists regarding the relationship between eating frequency and arteriosclerotic cardiovascular disease (ASCVD). Thus, the objective of this study was to explore the association of at-home eating (AHE) and out-of-home eating (OHE) frequency with 10-year ASCVD risk. Methods: A total of 23,014 participants were included from the Henan Rural Cohort Study. A face-to-face questionnaire was used to acquire data on the frequency of OHE and AHE. The relationship of OHE and AHE frequency with 10-year ASCVD risk was evaluated by logistic regression. Mediation analysis was conducted to evaluate whether BMI mediated the association of OHE and AHE frequency with 10-year ASCVD risk. Results: The adjusted OR and 95% CI of 10-year ASCVD risk for participants who ate out 7 or more times a week was 2.012 (1.666, 2.429) compared with participants who had OHE 0 times. Compared to those who had AHE ≤ 11 times, the adjusted OR and 95% CI for the participants eating every meal at home (21 times) was 0.611 (0.486, 0.769). The relationship of OHE and AHE frequency with 10-year ASCVD risk was mediated by BMI, and the proportion of BMI explained was 25.3% and 36.6%. Conclusions: The OHE frequency was associated with increased 10-year ASCVD risk, while AHE was related to decreased 10-year ASCVD risk, and BMI may play a partial mediating role in the relationship. Implementing health promotion strategies that promote AHE and discourage frequent OHE may prove to be an effective approach to preventing and controlling ASCVD. Trial registration number: ChiCTR-OOC-15006699 (2015–07-06). [ABSTRACT FROM AUTHOR]