BACKGROUND: Despite recommendations, TT (long-acting muscarinic antagonist [LAMA]+long-acting beta2-agonist [LABA]+inhaled corticosteroids) use across all COPD severities continues. Compare COPD-related, non-COPD pneumonia-related, and all-cause HCRU and clinical outcomes among maintenance-naïve COPD patients post-initiation of treatment with TIO+OLO (LAMA+LABA) versus TT in a U.S. Medicare Advantage population. This retrospective observational post-hoc analysis involved COPD patients ≥40 years initiating first-line TIO+OLO or TT between 01Jan2014-31Mar2018. 12-months pre-index and ≥30 days post-index continuous medical/pharmacy coverage was required. Patients were propensity score matched 1:1. Post-match cohorts (N=1,138 each) were balanced. TIO+OLO patients had significantly lower annualized COPD-related HCRU: mean inpatient stays (0.30 vs. 0.54; length of stay [LOS, days]: 1.82 vs. 3.80), office (4.27 vs 5.24), outpatient (1.82 vs. 3.45; all p<0.001), emergency room (ER; 0.34 vs 0.53; p=0.005) and other medical (3.43 vs. 4.66, p=0.004) visits. Non-COPD pneumonia-related mean inpatient stays (0.09 vs. 0.16, p=0.018; LOS: 0.84 vs. 1.66, p=0.047) and office visits (0.12 vs. 0.21, p=0.017) were significantly lower for TIO+OLO. TIO+OLO had lower all-cause HCRU for all settings and smaller percentages utilized the more expensive settings: inpatient (COPD-related: 16.45 vs. 30.59%; all-cause: 22.46 vs. 34.01%; both p≤0.002) and ER (COPD-related: 17.69 vs. 27.32%; all-cause: 37.05 vs. 49.33%; both p≤0.006). TIO+OLO had lower proportion with ≥1 severe exacerbations (8.11 vs. 16.75%; p=0.026), annualized mean count of severe exacerbations (0.13 vs. 0.21; p=0.015) and a reduced risk (but not significant) for ≥1 severe exacerbation (adjusted Hazard Ratio [HR]=0.72; 95% CI: 0.49-1.05; p=0.084) vs. TT. Proportions with pneumonia (13.48 vs. 19.69%; p=0.037) or pneumonia/acute bronchitis/bronchiolitis (22.16 vs. 29.42%; p=0.043) diagnoses were lower for TIO+OLO with 24% reduced risk of experiencing pneumonia/acute bronchitis/bronchiolitis diagnosis (adjusted HR=0.76; 95% CI: 0.60-0.97; p=0.026) compared with TT. These findings challenge the value of initiating COPD maintenance treatment with TT and provide real-world insight on the impact of recommendation-divergent prescribing practices.