ABSTRACTData about harms or benefits associated with the consumption of aspartame, a nonnutritive sweetener worldwide consumed, are still controversial. This systematic review and meta-analysis of randomized controlled clinical trials aimed to assess the effect of aspartame consumption on metabolic parameters related to diabetes and obesity. The search was performed on Cochrane, LILACS, PubMed, SCOPUS, Web of Science databases, and on a gray literature using Open Grey, Google Scholar, and ProQuest Dissertations & Theses Global. Searches across all databases were conducted from the earliest available date up to April 13, 2016, without date and language restrictions. Pooled mean differences were calculated using a random or fixed-effects model for heterogeneous and homogenous studies, respectively. Twenty-nine articles were included in qualitative synthesis and twelve, presenting numeric results, were used in meta-analysis. Fasting blood glucose (mmol/L), insulin levels (μU/mL), total cholesterol (mmol/L), triglycerides concentrations (mmol/L), high-density lipoprotein cholesterol (mmol/L), body weight (kg), and energy intake (MJ) were considered as the main outcomes in subjects that consumed aspartame, and results were presented as mean difference; % confidence interval, range. Aspartame consumption was not associated with alterations on blood glucose levels compared to control (−0.03 mmol/L; 95% CI, −0.21 to 0.14) or to sucrose (0.31 mmol/L; 95% CI, −0.05 to 0.67) and on insulin levels compared to control (0.13 μU/mL; 95% CI, −0.69 to 0.95) or to sucrose (2.54 μU/mL; 95% CI, −6.29 to 11.37). Total cholesterol was not affected by aspartame consumption compared to control (−0.02 mmol/L; 95% CI, −0.31 to 0.27) or to sucrose (−0.24 mmol/L; 95% CI, −0.89 to 0.42). Triglycerides concentrations were not affected by aspartame consumption compared to control (0.00 mmol/L; 95% CI, −0.04 to 0.05) or to sucrose (0.00 mmol/L; 95% CI, −0.09 to 0.09). High-density lipoprotein cholesterol serum levels were higher on aspartame compared to control (−0.03 mmol/L; 95% CI, −0.06 to −0.01) and lower on aspartame compared to sucrose (0.05 mmol/L; 95% CI, 0.02 to 0.09). Body weight did not change after aspartame consumption compared to control (5.00 kg; 95% CI, −1.56 to 11.56) or to sucrose (3.78 kg; 95% CI, −2.18 to 9.74). Energy intake was not altered by aspartame consumption compared to control (−0.49 MJ; 95% CI, −1.21 to 0.22) or to sucrose (−0.17 MJ; 95% CI, −2.03 to 1.69). Data concerning effects of aspartame on main metabolic variables associated to diabetes and obesity do not support a beneficial related to its consumption.