Background: With the aging population comes greater risks associated with polypharmacy, a significant public health problem. Objective: This study aimed to identify the prevalence of polypharmacy and its associated factors through Comprehensive Geriatric Assessment (CGA) among older adults treated in primary health care (PHC) in a large Brazilian urban center. Methods: We conducted a cross-sectional study with a random sampling of 400 older adults using primary health care. Polypharmacy was defined as the cumulative use of five or more daily medications. An assessment of a sociodemographic and health survey, fear of falling, and physical disabilities affecting activities of daily living and instrumental activities of daily living was conducted. Results: The mean age was 75.23 (SD: 8.53) years. The prevalence of polypharmacy and hyperpolypharmacy was 37% (n= 148) and 1% (n= 4), respectively. The adjusted logistic regression showed that participants with chronic non-communicable diseases (CNCDs) (OR = 9.24;p= 0.003), diabetes (OR = 1.93;p= 0.003), and obesity (OR = 2.15;p= 0.005) were associated with a greater propensity to use polypharmacy. Conclusion: Our results show that older adults with CNCDs, diabetes, and obesity were more likely to use polypharmacy. The results reinforce the importance of using CGA in clinical practice in PHC.