This is a small-scale exploratory trial from the Pro-Elderly study (“Protein Intake and Resistance Training in Aging”) aimed at gathering knowledge on the feasibility, efficacy and safety of co-supplementation with creatine and protein supplementation, in conjunction with resistance training, in older individuals with frailty. Methods: A 14-week, double-blind, randomized, parallel-group, placebo controlled exploratory trial was conducted between in Hamilton (New Zealand). The subjects were randomly assigned to compose either one of the following groups: 1) whey protein and creatine co-supplementation (WHEY+CR) or 2) whey protein supplementation (WHEY). All the subjects undertook a supervised exercise training program for 14 weeks and were assessed at baseline and after 14 weeks. The main dependent variables were muscle function (handgrip, timed-stands and timed-up-and go tests) and body composition (free fat mass, fat mass, and bone mass). Self-reported adverse events were recorded throughout the trial and blood parameters were assessed. Results: We found a main time-effect in handgrip (WHEY+CR = 26.65 ± 31.29; WHEY = 13.84 ± 14.93 Kg; p = 0.0005), timed-up-and-go (WHEY+CR = 11.20 ± 9.37; WHEY = -17.76 ± 21.74; p = 0.006 s), and timed-stands-test (WHEY+CR = 47.50 ± 35.54; WHEY = 46.87 ± 24.23 reps; p = 0.0001), suggesting that WHEY+CR and WHEY were similarly effective in improving muscle function. Exploratory analyses further suggested that most of the subjects experienced improvements in all muscle function tests. In addition, all of the subjects showed improvements in at least two of the three tests, regardless of their treatments. Neither within- nor between-group differences were detected in any of the body composition variables (all p > 0.05). No important adverse effect was observed and blood parameters remained unaltered. Conclusion: Co-supplementation with creatine and whey protein was tolerable and free of adverse events in older subjects with frailty undertaking resistance training. Furthermore creatine supplementation did not augment the adaptive effects of resistance training along with whey protein on body composition or muscle function in this population. Resistance training and co-supplementation with creatine and protein in older subjects with frailty iii This exploratory study will be insightful in designing a larger and more comprehensive randomized controlled trial to confirm or refute these findings. Clinicaltrials.gov: NCT01890382