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Objectives: To determine if anthropometric variables, body composition, medication and gender are associated with functional performance and to compare these variables between octogenarians with high and low functional performance. Methods: Observational, cross-sectional study. Weight, height, body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were evaluated. Handgrip strength (HGS) was assessed. Participants’ body composition was assessed by dual-energy X-ray absorptiometry (DXA) and functional performance by Short Physical Performance Battery (SPPB). A binomial logistic regression was performed. Results: One hundred and twenty-two octogenarians were included and separated into high and low function groups. The high function group showed lower values of WHtR (mean difference [MD] = 0.047, P = 0.025) and body fat (BF%) (MD = 3.54, P = 0.032) and higher values of apendicular skeletal muscle mass (ALM) (MD = 3.03, P = 0.001), HGS (MD = 6.11, P = 0.001) and SPPB score (MD = 4.20, P = 0.001). Women were more likely to be classified as low function (OR = 3.66, P = 0.002) and males showed 5.21 odds ratio (P = 0.021) of having high functional performance compared to females. Also, each decrease in age and medication use displayed 1.30 (P = 0.007) and 1.26 odds ratio increases (P = 0.008) in high functional performance. Conclusions: Older males display better functional performance than women, and decrements in age and medications increase the high functional performance odds ratio. Octogenarians with high functional performance displayed lower BF measurements and higher values of muscle mass and strength.