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Introduction: Insulin pen devices and disposable plastic insulin syringes are two common tools for insulin administration. This study aims to compare the simplicity, convenience, safety, and cost-effectiveness of insulin pens versus syringe devices in patients with type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study was conducted at 14 diabetes clinics throughout Bangladesh from November 2021 to April 2022 among adults with T2DM injecting insulin by pen devices or disposable insulin syringes at least once a day for at least one year by purposive sampling. The simplicity, convenience, and safety of insulin devices were assessed using a structured questionnaire, and the study subjects were scored based on their answers; higher scores indicated a poorer response. Total scores for simplicity, convenience, and safety were obtained by adding the scores for relevant components. Their average monthly medical expense and cost of insulin therapy were recorded. The median values of the total scores and monthly expenses were compared between pen devices and disposable syringe users. Results: 737 subjects were evaluated; 406 were pen users, and 331 were vial syringe users. The pen users had lower median scores for simplicity [6.0 (5.0–8.0) vs. 7.0 (5.0–9.0), p = 0.002], convenience [4.0 (3.0–6.0) vs. 5.0 (4.0–6.0), p < 0.001], and safety [7.0 (6.0–8.0) vs. 7.0 (6.0–9.0), p = 0.008] than vial syringe users. Pen devices were more expensive than vial syringes in terms of average medical expense per month [BDT 5000 (3500–7000) vs. 3000 (2000–5000), p < 0.001], the total cost of insulin therapy per month [BDT 2000 (1500–3000) vs. 1200 (800–1700), p < 0.001] and cost per unit of insulin used [BDT 2.08 (1.39–2.78) vs. 0.96 (0.64–1.39), p < 0.001]. Non-significant differences in favor of pens were observed in HbA1c levels [8.7 (7.8–10) vs. 8.9 (7.9–10)%, p = 0.607] and proportions of subjects having HbA1c < 7% (6.9 vs. 6.3%, p = 0.991). Conclusion: Insulin pens are simpler, more convenient, and safe but more expensive than vial syringes. Glycemic control is comparable between pen and syringe users. Long-term follow-up studies are needed to determine the clinical and economic impacts of such benefits of insulin pens. [ABSTRACT FROM AUTHOR]