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Background: The cardiovascular (CV) and metabolic health benefits or risks associated with consumption of multi-ingredient performance supplements (MIPS) in conjunction with periodized resistance training (RT) in resistance-trained men are unknown. This population is a major target audience for performance supplements, and therefore, the purpose of this study was to investigate the combined effect of RT and commercially available pre- and post-exercise performance supplements on CV health and body fat in resistance-trained men., Methods: Twenty-four resistance-trained men completed six weeks (three times/week) of periodized RT while either ingesting SHOT 15-min pre-exercise and SYN immediately post-exercise (multi-ingredient performance supplement group: MIPS) or an isocaloric maltodextrin placebo 15-min pre-exercise and immediately post-exercise (Placebo group). Before and after six weeks of RT and supplementation, resting heart rate (HR), blood pressure (BP), total body fat, android fat, gynoid fat, fat-free mass (FFM) and fasting blood measures of glucose, lipids, nitrate/nitrite (NOx), cortisol and high sensitivity C-reactive protein (hs-CRP) were measured. Statistical analysis was conducted using a one-way ANOVA for baseline differences and a 2 × 2 (group × time) repeated measures ANOVA and Tukey post-hoc tests where appropriate. Significance was set at p < 0.05., Results: There was no group × time interaction for HR, BP, blood glucose, lipids, NOx, hs-CRP, cortisol concentrations or body fat. However, there was a time effect where significant decreases in body fat (mean ± SD; MIPS: -1.2 ± 1.2%; Placebo: -0.9 ± 1.1%), android fat (MIPS: -1.8 ± 2.1%; Placebo: -1.6 ± 2.0%), and gynoid fat (MIPS: -1.3 ± 1.6%; Placebo: -1.0 ± 1.4%) for both groups were observed. FFM increased in both groups, and a group × time interaction was observed with MIPS increasing significantly more than the Placebo group (4.2% vs. 1.9%)., Conclusions: Six weeks of MIPS ingestion and periodized RT does not alter CV health parameters or blood indices of health or body fat more than a Placebo treatment in healthy, resistance-trained men. However, MIPS significantly increased FFM more than Placebo.