Resistance exercise training (RET) is a safe and effective way of enhancing or maintaining muscle mass in catabolic conditions (e.g. ageing, cancer, immobilization etc.). However, the heterogeneity of hypertrophic responses to RET is startling, with coefficients of variation often >100% (1-2). One possible explanation for this could be a [cumulative] blunting of muscle protein synthesis (MPS) after each bout of RE. Yet, there was no correlation between the degree of stimulation of anabolic signals or MPS after the first bout of RE and ensuing hypertrophy in younger individuals exposed to 16 weeks of RET (3). Nonetheless, whether bouts of RE beyond the first (i.e. where responses may be influenced by “muscle damage”) or the age of subjects impact this relationship remains unknown. To test this we recruited 44 individuals aged 18-65y (51.2±2.7y; body mass index (BMI) 25.4±0.7 kg/m-2). All subjects were screened, with exclusion for muscle wasting, metabolic, respiratory or cardiovascular disorders or history of ill health. Subjects were habitually active but did not participate in aerobic exercise and none had participated in RET in the previous 2y. Before and after RET (20-wks, 3x/wk, supervised, whole-body, 70% 1-RM) subjects underwent dual-energy X-ray absorptiometry (DXA; Lunar Prodigy II, GE Medical Systems) to quantify lean leg mass. Stable-isotope tracers (1,2-13C2 Leucine) (4) were I.V infused to quantify MPS (incorporation into myofibrillar proteins isolated from vastus lateralis biopsies) 2.5h after an acute bout of RE under fed conditions (Fortisip 4.25× basal metabolic rate); immunoblotting was used to quantify the phosphorylation of proteins controlling MPS (5). Data are presented as means±SEM analyzed by ANOVA and Pearson’s correlations with P<0.05 considered significant. The mean cohort increase in lean mass was (5.1±0.8%, P<0.01; range -3 to +27%). However, there were no relationships between hypertrophy and acute increases in MPS before (r=0.006, P=1.0) or after (r=0.004, P=0.7) RET; the same was true for AKT (before r=0.13, P=0.4; after r=0.17, P=0.3) and 4EBP1 phosphorylation (before r=0.05, P=0.8; after r=0.12, P=0.5). Upon splitting the cohort into age groupings of: young (18-40y, n=11), middle-aged (40-60y, n=16) and older (60-80y, n=17), we again failed to identify significant relationships. Likewise, dividing individuals by “responder status” for hypertrophy yielded no differences across quartiles. We conclude that while 20-wks RET was effective at inducing hypertrophy on average, there was significant heterogeneity unexplained by age or acute MPS/anabolic signaling -either before or after RET. Thus, metabolic and molecular responses to acute exercise are not predictive of hypertrophy and “responder status”; other approaches are needed to predict this.