BACKGROUND: There are limited data guiding the optimal inflation time for coronary drug-coated balloons. The aim of this study was to assess the clinical efficacy of an inflation time of ≥30 seconds compared with <30 seconds. METHODS: We conducted an observational nationwide analysis using the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify all patients undergoing percutaneous coronary intervention with drug-coated balloons and their inflation times. Outcomes were assessed at 1 year using Kaplan-Meier estimates and adjusted Cox regression. RESULTS: The <30-second group comprised 412 patients, and the ≥30-second group 10 826 patients. Patients in the <30-second group presented more often with lesions in proximal segments. After a 1-year follow-up, ≥30 seconds was associated with lower rates of target segment revascularization compared with <30 seconds (3.2% versus 6.4%, adjusted hazard ratio [HR], 0.47 [95% CI, 0.32-0.69], P≤0.001) and target vessel myocardial infarction (1.8% versus 5.3%, adjusted HR, 0.32 [95% CI, 0.21-0.50], P≤0.001). No difference was observed for all-cause mortality. CONCLUSIONS: In this analysis, including 11 238 patients undergoing PCI with drug-coated balloons, ≥30 second inflation time was associated with improved outcomes compared with a shorter inflation time.