Abstract Context Recently, the novel metabolic dysfunction-associated fatty liver disease (MAFLD) definition has been introduced. Objective To assess the relevance of MAFLD for mortality. Methods Single-center cohort-study using colorectal cancer screening program involving 4718 subjects aged 45 to 80 who were grouped according to their body mass index (BMI) and the presence or absence of MAFLD. Mortality was compared among these groups by performing a systematic read-out of the national health insurance system, fatty liver (FL) was diagnosed using ultrasound. Results Overall prevalence of FL was 47.9%: 1200 (25.4%) patients were lean (BMI < 25 kg/m2) and did not have MAFLD, 73 (1.5%) patients were lean and had nonalcoholic fatty liver disease but did not fulfill criteria for MAFLD, and 221 (4.7%) patients were lean and fulfilled criteria for MAFLD. Additionally, 1043 (22.1%) and 925 (19.6%) subjects had MAFLD with overweight (BMI 25-30 kg/m2) and obesity (BMI ≥ 30 kg/m2), respectively, while 1041 (22.1%) and 215 (4.6%) had overweight and obesity, respectively, without FL. During a median follow-up of 7.5 (interquartile range: 4.0-9.6) years, 278 deaths (5.9%) occurred. Of these, 98 (2.1%) were cancer-related, 65 (1.4%) were cardiovascular, and 17 (0.4%) were liver-related. Overall survival was similar between patient strata (after 5 years: 93.9%-98.2%) with lean MAFLD having the numerically worst survival. Although lean and overweight patients with MAFLD had a numerically worse outcome compared to their non-MAFLD counterparts, this association was driven by age and metabolic comorbidities (predominantly diabetes) rather than the presence of MAFLD. Conclusion Presence of MAFLD does not increase mortality in a cohort of individuals aged 45 to 80 years.