OBJECTIVES To investigate whether patients with type-2 Diabetes Melittus (T2DM) who gained ≥5% of their bodyweight over the course of one year experienced changes in health-related quality of life (HRQoL) and work impairment relative to those who lost ≥5% of their bodyweight. METHODS Data were taken from the 2006 and 2007 National Health & Wellness Survey, an annual, cross-sectional, Internet survey of US adults. All patients in survey with T2DM whose 2006-2007 weight gain was ≥5% of their bodyweight (n=300) were compared to those whose weight loss was ≥5% of their bodyweight (n=330) on levels of HRQoL (assessed with the SF-8 and SF-12 for 2006 and 2007, respectively) and levels of work impairment (assessed with the Work Productivity and Activity Impairment Questionnaire (WPAI)) in a series of multiple regressions, controlling for demographics, volitional weight loss (whether or not respondents were taking steps to lose weight), and comorbidities. RESULTS It was shown that weight gain was associated with significantly lower levels of the SF-12 Physical Component Summary (mean score (M)=39.6 vs. M=41.5, p<0.01). Among obese respondents, this effect was amplified (M=37.6 vs. M=40.3, p<0.01). No significant differences were found between T2DM patients who gained ≥5% of their weight and those who lost ≥5% of their weight on Mental Component Summary (M=48.6 vs. M=47.9, p=0.34), absenteeism (mean impairment (M)=4.6% vs. M=1.8%, p=0.32), presenteeism (M=18.9% vs. M=14.3%, p=0.26), total work impairment (M=20.1% vs. M=16.6%, p=0.46), or activity impairment (M=33.8% vs. M=31.4%, p=0.22), though most effects were in the expected direction. CONCLUSIONS T2DM patients who gained weight, especially for obese individuals, reported significantly lower levels of HRQoL relative to those who lost weight. Treatments that avoid weight gain and/or promote weight loss could have a beneficial impact beyond HgbA1c for T2DM patients.