OBJECTIVES: Studies suggest that “pen” devices offer advantages over traditional vial and syringe method for insulin administration. Our purpose was to evaluate their efficacy safety and patient preference through a systematic review and meta-analysis. METHODS: A systematic review was performed using an expert-approved PICO question, in 8 different databases. References were screened by two independent investigators. Primary observational or experimental full articles comparing pen devices with vial and syringes for insulin administration in adults with diabetes mellitus were included (except gestational diabetes). Manual search for additional references was performed on selected articles. Risk of bias was evaluated using the appropriate tools. We collected data on glycosylated hemoglobin (HbA1c), hypoglycemia, adherence, persistence, patient preference and quality of life. When possible, meta-analysis was performed, evaluating the presence of heterogeneity and risk of publication bias. Otherwise, descriptive analysis of the available data was done. RESULTS: Of the 10.348 original references scanned, 17 studies were finally selected, 7 experimental and 10 analytical. The population included was mainly adults, with type 2 diabetes. Important risk of bias was found in all of the articles, particularly the experimental ones. Meta-analysis was performed for glycemic control, hypoglycemia, adherence and persistence. Pen devices showed better results in mean HbA1c change, frequency of hypoglycemia, adherence and persistence compared to vial and syringes. No difference was observed in number of patients achieving <7% of HbA1c. Studies regarding preference showed a clear tendency favorable to pen devices, but measurement methods were generally not well validated. One study on quality of life showed improvements in some subscales of SF-36. CONCLUSIONS: There is evidence that pen devices offer benefits regarding glycemic control, hypoglycemia, adherence, persistence, patient preference and quality of life compared to vial and syringes for insulin administration. However, data had considerable risk of bias, more methodologically sound studies are needed.