The objective of these two studies was to assess patient acceptance and feature preferences of the new Lilly 3.0 ml pre-filled pen. A total of 701 patients with diabetes mellitus, who required insulin, were treated for 4-6 weeks with the pre-filled pen. Patient acceptance and treatment preferences were assessed by a questionnaire completed at the end of the study period. Patients with type 1 or type 2 diabetes mellitus from South Africa (n = 371) and Croatia (n = 330) were enrolled in the study. The mean age was 51.6 years (range: 18-81), and gender was 359 males and 342 females. Prior to the study, patients in South Africa (SA) had used the Novo Actraphane (Novo Nordisk, Bagsvaerd, Denmark) pen set, and patients in Croatia (C) had used NovoPen 1 or 2 (Novo Nordisk, Bagsvaerd, Denmark) (38.8%), NovoPen 3 (Novo Nordisk, Bagsvaerd, Denmark) (28.8%), B-D Pen (Becton-Dickinson, Franklin Lakes, New Jersey, USA) (18.8%), needle/syringe (10.0%), oral hypoglycaemic agents (2.1%), or unknown (1.5%). The new Lilly 3.0 ml pre-filled pen features that were rated by respondents as good to excellent on a five-point rating scale included: cartridge visibility (C = 94%, SA = 83%), ease of dose correction (C = 92%, SA = 85%), dialling of the dose (C = 89%, SA = 81%), turning of the dose knob (C = 84%, SA = 82%) and attaching needles (C = 92%, SA = 78%). Most respondents (C = 78%, SA = 75%) preferred single-unit versus two-unit dosage increments. Overall, 76% of patients in Croatia and 80% in South Africa preferred the Lilly 3.0 ml pre-filled pen to their previous delivery device; 84% and 87% of patients, respectively, would recommend the pen to another patient. Also, the majority of patients in both trials rated the new Lilly 3.0 ml pre-filled pen as being more convenient and easier to use, and indicated that it represented a significant or modest improvement over their previous insulin injection method. The results of this study confirm that the new Lilly 3.0 ml pre-filled pen is widely accepted and preferred by patients using both reusable and pre-filled devices.