Introduction Insulin degludec/insulin aspart (IDegAsp) provides effective glycaemic control with an acceptable safety profile in Japanese patients with diabetes in randomised clinical trials. This post-marketing surveillance study assessed long-term safety and clinical outcomes with IDegAsp in a Japanese real-world setting. Methods Multicentre, prospective, observational, open-label, single-arm study of Japanese patients with diabetes requiring insulin therapy, who had switched to IDegAsp at their treating physician’s discretion in clinical practice. One year after initiating IDegAsp, incidence of adverse events (AEs primary endpoint), serious AEs, adverse drug reactions (ADRs), and severe hypoglycaemia (secondary safety endpoints) were assessed in the safety analysis set (SAS). Secondary effectiveness endpoints were change from baseline in glycated haemoglobin (HbA 1c ) and fasting plasma glucose (FPG) in the effectiveness analysis set (EAS). Results Overall, 1321 patients were included (SAS, n  = 1321; EAS, n  = 1285); 4.2% with type 1 diabetes, 95.2% with type 2 diabetes, 0.7% with other/unknown diabetes type. In total, 204 AEs were reported in 132 patients (10.0% of the SAS), at a rate 95% confidence interval (CI) of 16.2 events/100 patient-years of exposure (PYE) 14.0; 18.4. By preferred term, ‘hypoglycaemia’ was the most frequent AE (45 events in 31 patients 2.3%; rate 95% CI 3.6 events/100 PYE 2.5; 4.6). Serious AEs occurred in 4.2% of patients (rate 95% CI 5.7 events/100 PYE 4.4; 7.0), and ADRs in 3.1% (rate 95% CI 4.6 reactions/100 PYE 3.4; 5.8). Six events of severe hypoglycaemia were reported in five patients (0.4%; rate 95% CI 0.5 events/100 PYE 0.1; 0.9). Change from baseline to 1 year was − 0.51% and − 32.1 mg/dL for HbA 1c and FPG, respectively ( P  < 0.0001 for both). Conclusion In Japanese patients with diabetes, initiation of IDegAsp in real-world clinical practice was well tolerated, with no new safety signals, and associated with improved glycaemic control after 1 year. Trial Registration ClinicalTrials.gov identifier, NCT02821052.