AbstractObjectiveThe study objective was to examine associations of relative fat mass (RFM) and BMI with all‐cause mortality in the Dutch general population and to investigate whether additional adjustment for muscle mass strengthened these associations.MethodsA total of 8433 community‐dwelling adults from the PREVEND general population cohort (1997–1998) were included. Linear regression models were used to examine associations of RFM and BMI with 24‐h urinary creatinine excretion, a marker of total muscle mass. Cox regression models were used to examine associations of RFM and BMI with all‐cause mortality.ResultsThe mean age of the cohort was 49.8 years (range: 28.8–75.7 years), and 49.9% (n = 4209) were women. In age‐ and sex‐adjusted models, both RFM and BMI were associated with total muscle mass (24‐h urinary creatinine excretion), and these associations were stronger with BMI (standardized beta [Sβ]RFM: 0.29; 95% CI: 0.27–0.31 vs. SβBMI: 0.38; 95% CI: 0.36–0.40; pdifference < 0.001). During a median follow‐up period of 18.4 years, 1640 deaths (19.4%) occurred. In age‐ and sex‐adjusted models, RFM was significantly associated with all‐cause mortality (hazard ratio per 1‐SD [HRRFM]: 1.16; 95% CI: 1.09–1.24), whereas BMI was not (HRBMI: 1.04; 95% CI: 0.99–1.10). After additional adjustment for muscle mass, associations of both RFM and BMI with all‐cause mortality increased in magnitude (HRRFM: 1.24; 95% CI: 1.16–1.32 and HRBMI: 1.12; 95% CI: 1.06–1.19). Results were broadly similar in multivariable adjusted models.ConclusionsIn the general population, a higher RFM was significantly associated with mortality risk, whereas a higher BMI was not. Adjusting for total muscle mass increased the strength of associations of both RFM and BMI with all‐cause mortality.