This study assessed the psychometric properties of the SF-36 questionnaire in a sample of 4344 Peruvian people aged 15 to 64 years. Internal consistency reliability was estimated using Cronbach’s α coefficient, construct validity by known-groups comparison defined with respect to key sociodemographic characteristics, and factor structure by confirmatory factor analysis (CFA) at item level. Cronbach’s α coefficient for the full questionnaire was 0.82 and ranged between 0.66 and 0.92 by scales. The 8 scales discriminated well between sexes, age, and socioeconomic groups. CFA showed that a model with 8 first-order factors and 2 second-order factors (namely, physical and mental health) was a feasible representation of the SF-36 factor structure and had better fit to data than alternative factor structures. The SF-36 showed appropriate psychometric properties regarding internal consistency, construct validity, and factor structure when tested in Peru. Future studies should focus on testing other psychometric properties of the SF-36, such as convergent and discriminant validity, test-retest reliability, and sensitivity to change.