BACKGROUND: The association of a healthy lifestyle and the American Heart Association (AHA) Life's Essential 8 (LE8) score with the risk of new-onset nonalcoholic fatty liver disease (NAFLD) remains uncertain. We aimed to explore the associations between a healthy lifestyle and higher LE8 scores with new-onset severe NAFLD in the general population. METHODS: 266,645 participants without prior liver diseases were included from the UK Biobank. A healthy lifestyle was determined based on body mass index, smoking, alcohol consumption, physical activity, sleep duration, and diet. LE8 score was generated from 8 metrics according to the AHA cardiovascular health (CVH) advisory, varying from 0 to 100 scores. The primary study outcome was new-onset severe NAFLD. The study outcomes were ascertained by hospital inpatient data, cancer registry, and death register records. RESULTS: During a median follow-up of 11.9 years, 2284(0.9 %) participants developed severe NAFLD. Compared with those with a poor lifestyle, participants with intermediate (HR, 0.60; 95%CI: 0.55-0.67), or ideal (HR, 0.20; 95%CI: 0.15-0.27) lifestyles had a significantly lower risk of new-onset severe NAFLD. Compared to the low CVH group (LE8 scores: 0-49), the moderate (scores:50-79) (HR, 0.43; 95%CI: 0.39-0.48) and high CVH (scores:80-100) (HR, 0.10; 95%CI: 0.07-0.14) group had a significantly lower risk of new-onset severe NAFLD. Accordingly, adhering to a healthy lifestyle and attaining a high CVH in all individuals could prevent 66.8 % (95%CI: 58.5-75.1 %) and 77.3 % (95%CI:70.4-84.2 %) of severe NAFLD, respectively. Genetic risks of NAFLD did not modify these associations. CONCLUSION: A favorable lifestyle and a higher LE8 score were significantly associated with a lower risk of new-onset severe NAFLD, independent of genetic risks of NAFLD.