Previous real-world evidence suggests that prompt versus delayed initiation of single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) following an exacerbation results in improved clinical outcomes for patients with chronic obstructive pulmonary disease (COPD). This prior study was conducted in the first 2years following FF/UMEC/VI approval, representing early trends. The current updated analysis aims to further elucidate the real-world evidence for FF/UMEC/VI. This was a retrospective cohort study using the IQVIA PharMetrics® Plus database. Patients with COPD initiating SITT with FF/UMEC/VI within 6months of an exacerbation (index date) were classified as prompt (≤ 30days following exacerbation) or delayed (31-180days) initiators. The baseline period comprised the 12months prior to index. Inverse probability of treatment weighting was used to balance differences in baseline characteristics between cohorts. COPD exacerbations, hospital readmission rates, and healthcare costs were compared between cohorts post-index. Overall, 5421 patients (prompt, 2057; delayed, 3364) were included. After weighting, baseline characteristics were well balanced between cohorts. For up to 12months post-index, prompt initiators of FF/UMEC/VI had significantly lower rates of exacerbations per person-year versus delayed initiators (0.74 vs. 1.06; rate ratio 0.70, 95% confidence interval [CI] 0.64-0.77; P < 0.001). A 1-day delay in FF/UMEC/VI initiation was associated with a 0.31% increase in the rate of exacerbations. At 90days post-index, Kaplan-Meier rates of all-cause (hazard ratio [HR] 0.62, 95%CI 0.45-0.86; P = 0.004) and COPD-related (HR 0.58, 95%CI 0.35-0.98; P = 0.042) hospital readmissions were significantly lower in the prompt versus delayed cohort. Total COPD-related healthcare costs per person per year were significantly lower for patients in the prompt versus delayed cohort. Healthcare providers should consider the positive impact of prompt FF/UMEC/VI initiation on exacerbation rate, hospital readmission rate, and costs when treating patients with COPD at risk of exacerbations.