Poor medication adherence compromises treatment efficacy and adversely affects patients’ clinical outcomes. This study aims to assess (1) multiple medication adherence to the most common drug classes chronically prescribed to older people, (2) the factors associated, and (3) the clinical outcomes. This retrospective cohort study included 122,655 community-dwelling patients aged 65–94 years old, newly exposed to chronic polypharmacy, and recorded in the Lombardy Region (northern Italy) administrative database from 2016 to 2018. Multiple medication adherence was assessed for drugs for diabetes, antithrombotics, antihypertensives, statins, and bisphosphonates, by calculating the daily polypharmacy possession ratio (DPPR). One-year mortality, nursing home, emergency department (ED), and hospital admission rates were calculated for 2019. The most prescribed drugs were antihypertensives (89.0%). The mean (std.dev) DPPR was 82.9% (15.6). Being female (OR = 0.85, 95%CI: 0.84–0.86), age ≥85 years (OR = 0.77, 95%CI: 0.76–0.79), and multimorbidity (≥4 diseases, OR = 0.88, 95%CI: 0.86–0.90) were associated with lower medication adherence. A higher DPPR was associated with clinical outcomes—in particular, improved survival (HR = 0.93 for 10/100-point increase, 95%CI: 0.92–0.94) and lower incidence in nursing home admissions (SDHR = 0.95, 95%CI: 0.93–0.97). Adherence to the most common chronic drugs co-prescribed to the older population was high. Better multiple medication adherence was associated with better clinical outcomes.