OBJECTIVES:   Both biphasic human insulin 30 (BHI30) and biphasic insulin aspart (BIAsp30) serve an effective treatment option in patients with T2DM and their relative efficacy has been investigated in randomized clinical trials (RCTs). The aim of our analysis was to compare efficacy and safety of BIAsp30 with BHI30 on the basis of non-interventional trials. METHODS: Systematic search in PubMed, Medline and CENTRAL was carried out until November 2011. Non-interventional trials comparing either BIAsp30 with BHI30 in a parallel design or assessing a replacement therapy with one insulin preparation after suboptimal response to the other were included. RESULTS: Eight studies met the inclusion criteria; three compared directly BIAsp30 with BHI30, five assessed BIAsp30 after suboptimal treatment with BHI30. No studies evaluating BHI30 after BIAsp30 were identified. Meta-analysis of parallel studies demonstrated superiority of BIAsp30 over BHI30 with respect to the reduction of HbA1c (3 studies; WMD = -0.16% [-0.24; -0.08]) without increased risk of hypoglycemic episodes. Switching from BHI30 to BIAsp30 was associated with noticeable improvement in HbA1c level (3 studies; WMD = -1.69% [-1.94; -1.45]), fasting glucose (2 studies; -3.20 mmol/l [-3.75; -2.65]) and post-prandial glucose level (2 studies; WMD = -4.66 mmol/l [-4.74; -4.58]). The largest study demonstrated that the use of BIAsp30 instead of BHI30 revealed statistically significant reduction in the incidence of both minor (MD = -5.7 episodes/patient/year; p<0.0001) and major hypoglycemic episodes (MD = -0.331; p<0.0001). BIAsp 30 was not associated with a weight gain either in parallel design nor in studies assessing sequential treatment. CONCLUSIONS: In this analysis, including real clinical practice studies BIAsp30 was more effective than BHI30 in the control of T2DM. Additionally, BIAsp30 was a good alternative for patients with failure or suboptimal response to previous insulin therapy with BHI30.