OBJECTIVES: The two most commonly used insulin delivery devices, pens and syringes, have comparable safety profiles and efficacy under similar use conditions.  Therefore, the decision regarding the preferred device must be based on other considerations such as treatment satisfaction, treatment adherence, health-related quality of life (HRQoL), health care expenditure and utilization. METHODS: A literature search was conducted of published articles in peer reviewed journals listed in the US National Library of Medicine’s PubMed (1948-present), DIALOG including PsychInfo (1887-Present), EMCARE (nursing lit., 1995-Present), BIOSIS (1993-Present), EMBASE (Excerpta Medica, 1974-Present), SciSearch (1990-Present) and MEDLINE. Relevant manuscripts were classified into subcategories based on the major focus of the article reviewed and then subcategories were collapsed into major categories: treatment satisfaction, treatment adherence, HRQoL, and health care expenditure and utilization. RESULTS: A total of 135 publications were reviewed for inclusion of which 73 manuscripts and 9 conference abstracts/poster were deemed relevant and reviewed in depth.   Seventeen reported findings from clinical trials and 13 were review articles. There is substantial evidence demonstrating the superior benefits of pens over syringes. Treatment satisfaction and patient preference for pens over syringes was widely reported and patients reported that pens provided them with increased confidence in dose, ability to self-inject, superior convenience and overall ease of use.  Pen users reported better treatment adherence and fewer missed insulin doses which may account for the reported better HbA1c control than with syringe. Health care expenditure and utilization were higher in the short term for pens, however, these expenditures were minor in comparison with long-term savings that result from improved decreases in hospitalizations, incidence of side effects, physician visits and emergency department visits. CONCLUSIONS: Long and short term diabetes management should benefit from the choice of pen as the insulin delivery method based on PRO outcomes and long term cost effectiveness.