AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%. RESULTS: At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, -1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels.