Creatine (Cr) supplementation increases muscle mass and strength. Arginine alpha-ketoglutarate (AAKG) acts as a precursor for nitric oxide production, and has the potential to improve blood flow and nutrient delivery (i.e., creatine) to exercising muscles. The purpose of this study was to compare supplementation with Cr + AAKG to Cr alone or placebo during heavy resistance-exercise (RE) on lean tissue mass and muscle strength. Young healthy adults (n=23, 14 male, 9 female, ~23 years) were randomized (double blind) to one of three isocaloric treatment conditions: (1) Cr + AAKG (0.1g.kg-1 body mass Cr + 0.75g.kg-1 AAKG, n=8, 5 male, 3 female), (2) Cr (0.1g.kg-1 , n=8; 5 male, 3 female), or (3) placebo (1g.kg-1 sucrose, n=7, 4 male, 3 female) for 6 weeks. Prior to and following supplementation and RE, measurements were taken for lean tissue mass (under-water weighing) and muscle strength (1 repetition maximum leg press and bench press). Repeated measures ANOVA showed there were no differences (mean ± SD) between groups for changes in body mass (Cr + AAKG: 83.8±9→84.1±11kg, 0.4%; Cr: 77.9±11→77.5±9kg, -0.2%; placebo: 80.1±13→80.8±10kg, 0.9%), lean tissue mass (Cr + AAKG: 68.1±10→70.1±12kg, 2.9%; Cr: 61.2±11→62.1±9.1kg, 1.5%; placebo: 66.2±11→66.7±10kg, 0.8%) or leg press strength (Cr + AAKG: 267±68→371±91kg, 39%; Cr: 271±90→330.1±73kg, 22%%; placebo: 261±125→350±120kg, 34%). The Cr + AAKG group experienced a greater increase in bench press strength (p<0.05) compared to Cr and placebo (Cr + AAKG: 105±14→125±16kg, 19%; Cr: 79±11→87.2±19kg, 10.3%%; placebo: 84±8→94±11kg, 11%). These results suggest that Cr + AAKG supplementation during short-term heavy resistance-exercise may result in small improvements in upper body muscle strength in young adults.