OBJECTIVE To evaluate the effects of demographics and hormonal variations on knee muscle performance in patients with acromegaly and develop explanatory models of peripheral muscle function in these individuals. METHODS This was a cross-sectional study in which 53 acromegalics and 27 healthy subjects underwent knee isokinetic dynamometry to evaluate the peak torque value for leg extension at 75°/s (PTE75) and 240°/s (PTE240). Separate multivariable linear regression models for the prediction of PTE75 and PTE240 were tested using variables commonly used as predictors in the clinical setting and other specific variables related to acromegaly. RESULTS The final prediction model for PTE75 (R(2)=0.888; adjusted R(2)=0.820, SE of bias=16.2Nm, p<0.001) was -0.221×growth hormone+36.791×sexmale=1-27.407×statusactive=1-0.690×age+148.071. The final prediction model for PTE240 (R(2)=0.816; adjusted R(2)=0.805, SE of bias=8.8Nm, p<0.001) was -0.174×growth hormone+12.522×sexmale=1-0.520×age+98.099. CONCLUSIONS In acromegalics, high growth hormone levels, female gender, and older age are associated with reduced muscle strength and endurance. Additionally, active disease negatively affects peripheral muscle strength in these patients.