Introduction <p>Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) is approved for the treatment of asthma in Japan. Currently, data on the safety, particularly on cardiovascular (CV) risk, and effectiveness of FF/UMEC/VI in Japanese real-world clinical practice are limited.</p> Methods <p>This prospective, multicenter, post-marketing surveillance was undertaken to assess the safety and effectiveness of once-daily single-inhaler triple therapy FF/UMEC/VI (100/62.5/25 or 200/62.5/25 mcg) newly initiated in patients with asthma in Japan between July 2021 and November 2023. The observation period was 1&#xa0;year after the first FF/UMEC/VI prescription or until termination or withdrawal from treatment. Safety was assessed by incidence of adverse drug reactions (ADRs) including CV events as safety specification to be checked due to risk associated with use of UMEC. Overall assessment of effectiveness (based on lung function, asthma symptoms, and proportion of patients with exacerbation events) and asthma management status was assessed by the investigator.</p> Results <p>Overall, 8.4% (24/286) of patients reported an ADR. The most common ADRs were cough and dysphonia (each 7/286). Urinary retention was reported as a serious ADR in 1 patient, and CV event palpitations were reported in 2 patients. FF/UMEC/VI treatment was deemed effective in 92.5% (260/281) of patients in the effectiveness analysis. Lung function and asthma control test results improved following initiation of FF/UMEC/VI. In the 1&#xa0;year after initiation, 6.2% (11/178) of patients experienced exacerbation events, while 25.8% (46/178) of patients experienced exacerbation events prior to initiation.</p> Conclusion <p>FF/UMEC/VI was well tolerated and effective in the treatment of patients with asthma in Japan. ADRs were reported in 8.4% of patients and the incidence of CV events was low. No new safety concerns were identified.</p>