||The development of inhaled insulin has made the evaluation of non-medical, patient-centered influences of treatment adherence more important when weighing risks and benefits of diabetes therapies, especially for persons over age 65. To evaluate barriers to insulin use in this population we studied 81 type 2 DM patients aged 65 years and older from 32 centers in the US and Canada randomized to either pre-meal inhaled human insulin plus bedtime long-acting insulin (INH; N=44) or at least two daily injections of mixed regular/NPH insulin (SC; N=37) for 24 wks. At baseline, patients were 70% male and had mean (±SD) age = 70.0±3.8 yrs, BMI = 29.6±3.8 kg/m?2, HbA1c = 7.9±1.0%, and DM duration = 18.0±9.9 yrs. Outcome measures were self-reported satisfaction, quality of life (QOL), adherence barriers (390 questions total) at baseline, week 6, 12, 20 and 24; HbA1c, and adverse events. Baseline-adjusted, endpoint HbA1c was comparable for INH and SC (7.1 vs 7.2%, P=0.5). During treatment, overall satisfaction (0100) adjusted for baseline was higher for INH vs SC (mean ± SE: 81.8±1.0 vs 64.5±1.1), as were overall QOL (100600) (492.8±3.2 vs 475.9±3.5) and adherence to insulin use (0100) (80.2±1.2 vs 62.1±1.3); all P<0.0001 between groups. All satisfaction subscales (advocacy, burden, convenience, perceived efficacy, flexibility, general satisfaction, hassle, life interference, pain, preference, side effects, social) favored INH (P<0.01), as did QOL scales of mental health (P=0.001) and cognitive acuity (P=0.028 ). Compared to their baseline insulin regimen, 93% of INH users preferred inhaled insulin overall, with the highest ratings given for ease of use, use in public, sense of well being (all 93%), and easier disposal, more meal flexibility and convenience (all 91%). Conclusions: Inhaled insulin increased acceptance with insulin use in persons with type 2 DM aged 65 years and older by improving satisfaction and QOL, and by reducing adherence barriers to insulin use.