OBJECTIVES: Clinical wisdom assumes that treatment satisfaction (TS)with insulin improves with fewer injections and side effects. We examined the relationships between TS, patient characteristics (age, gender, ethnicity, weight, co-morbidities, diabetes duration) and treatment outcomes (HbA1c, number of daily injections, weight gain, hypoglycemic events).METHODS: Baseline and 28 week RCT data comparing efficacy and safety of Biphasic Insulin Aspart 70/30 (BIAsp 70/30,NovoMix® 30/NovologMix® 70/30) vs. insulin glargine in type 2 diabetics(n=240) were analyzed. Subjects completed the Insulin Treatment Satisfaction Questionnaire (ITSQ - overall TS and 5 domains: Lifestyle Flexibility, Hypoglycemic Control, Glycemic Control, Device Satisfaction, Inconvenience of Regimen). Regression analyses examined the relationship between TS, patient/disease characteristic and outcomes. Significant factors were examined together by multivariate regression analyses. RESULTS: The presence of diabetes-related co-morbidities, notably neuropathy predicted overall TS and 3/5 domains (p<0.05). Retinopathy impacted Device Satisfaction, age was related to Lifestyle Flexibility (p<0.05). No other baseline patient/disease characteristic impacted TS. Lowered HbA1c impacted overall TS, and 3/5 domains (p<0.05). Number of hypoglycemic events impacted Hypoglycemic Control, timing of the event was related to overall TS and all domains (p<0.001). Weight gain, number of daily injections and treatment group did not impact TS despite the presence of significant treatment group difference. When all significant factors were examined together, HbA1c reduction and neuropathy maintained their impacts on TS. The impact of the number of hypoglycemic events remained only for Hypoglycemic Control, while timing of the hypoglycemic event impacted overall TS and 3/5 domains (p<0.01). CONCLUSION: Contrary to clinical wisdom, the number of daily injections may not negatively impact TS when balanced by significant HbA1c treatment benefits. Factors impacting TS when examined independently did not always exert the same significant influence when assessed in combination with other factors. Clinicians should judge the balance between positive and negative treatment outcomes before considering treatment options.