To evaluate the effectiveness, comfort, and ease of use of insulin pen injections with a 31-gauge, 8-mm needle. In 50 study subjects (24 patients with type 1 insulin-dependent diabetes and 26 insulin-using patients with type 2 diabetes), we assessed the delivery of insulin, residual insulin leakage, glycemic control, plunger depression pressure, and perceived pain associated with the B-D 31-gauge, 8-mm pen needles in comparison with the B-D conventional 30-gauge, 8-mm pen needles, while the patient used their own insulin pens (Novo or B-D). The study subjects injected their usual dose of regular and NPH insulin using the 30-gauge, 8-mm needle during the first 3 weeks of the study. This period was followed by two 3-week crossover segments of the study with either needle assigned in random sequence. No statistically significant differences were noted in glycemic control or perceived pain of injection between the two needles. The interaction between the two needles and the two insulin pen brands on glycemic control was not statistically significant. Plunger depression pressure increased with the increase in the gauge of the needle and with increases in size of dose of injected insulin (P<0.01). B-D pen users reported lower plunger pressure ratings in comparison with Novo pen users (P<0.01), regardless of the needle type and dose range. Both the insulin pen type and the needle type individually had statistically significant (P<0.01) effects on the residual insulin leakage from the needle tip after injection; however, their interaction was not statistically significant. Insulin doses greater than 30 units were associated with increased leakage (P<0.01). As needle retention time decreased, residual insulin leakage from the needle tip after injection increased (P<0.01), regardless of the needle used. The 31-gauge insulin pen needles are safe and effective for the delivery of insulin. With both 30-gauge and 31-gauge needles, attention to injection technique is essential to ensure complete delivery of insulin, particularly with administration of large doses.