To study assessed adherence to 11 chronic medications and one medication class with high medical necessity in people with cognitive impairment (CIM) and identified clinical characteristics associated with nonadherence. This was a retrospective cohort study. 180-day adherence was calculated as the percent of days covered (PDC). Multi-variable logistic regression modeling was used to identify clinical factors associated with a PDC less than 80% (ie, nonadherence) to one or more studied chronic medication(s). Primary care in an integrated health care delivery system. People with CIM 65 years of age or older who were dispensed five or more chronic medications in one month between March 1, 2019, and October 31, 2019. Overall, the 1,109 patients included were older (mean age = 79.8 years of age), female (54.1%), White (78.6%), had a high burden of chronic disease, and 396 (35.7%) were nonadherent to one or more study medication(s). Two medications (tiotropium and venlafaxine) and one medication class (direct oral anticoagulants) had a mean PDC less than 80%. Alzheimer's disease and related dementias (ADRD), chronic pain, chronic obstructive pulmonary disease (COPD), male, nonwhite race, and one or more mental health visits were associated independently with nonadherence. Chronic pain, COPD, ADRD, male sex, nonwhite race, and mental health care use were associated with nonadherence. These findings can help guide clinicians as they navigate medication therapy in people with CIM.