Real-world asthma control data among patients initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) are limited. This study assessed rescue medication use and asthma-related exacerbations in patients with asthma before and after initiating single-inhaler FF/UMEC/VI using administrative claims data. This retrospective, pre-post cohort study analyzed data from the IQVIA PharMetrics Plus database (September 18, 2016‒March 31, 2020). Patients aged ≥18 years that had ≥1 dispensing of single-inhaler FF/UMEC/VI 100/62.5/25 mcg (first dispensing = index date), ≥12 months of continuous health insurance enrollment prior to (pre-treatment) and following (post-treatment) FF/UMEC/VI initiation and ≥1 diagnosis of asthma during the pre-treatment period or on the index date were included. The primary endpoint was the number of oral corticosteroid (OCS) dispensings per patient per year during pre- and post-treatment periods. Secondary endpoints included asthma-related exacerbation rates and short-acting β -agonist (SABA) use. Comparisons between pre- and post-treatment periods were made using risk and rate ratios. Overall, 890 patients with asthma initiating treatment with FF/UMEC/VI were included. The most recently dispensed controller medications prior to FF/UMEC/VI initiation were inhaled corticosteroids/long-acting β -agonists (33.5%) and leukotriene modifiers (33.0%). Patients had a 29% reduction in the number of OCS dispensings (rate ratio 95% confidence interval (CI): 0.71 0.65, 0.77, P < 0.001) during post-treatment versus pre-treatment, with a 23% reduction in the proportion of patients with ≥1 OCS dispensing post-treatment (risk ratio 95% CI: 0.77 0.73, 0.82, P < 0.001). Significant reductions in rates (rate ratio 95% CI) of asthma-related exacerbations (0.59 0.52, 0.67, P < 0.001) and SABA use (0.80 0.74, 0.86, P < 0.001) were also observed. In this real-world study, patients with asthma had significantly lower OCS use, asthma-related exacerbations, and SABA use following treatment initiation with FF/UMEC/VI compared with their pre-treatment period. These results suggest better asthma control following initiation of FF/UMEC/VI in a routine clinical practice setting.