Objective: Many patients treated for primary hypothyroidism have an unexplained reduced quality of life (QOL). We studied the relation between QOL and various parameters in treated hypothyroid patients. Design and methods: QOL analysis was done in 90 consecutive patients (77.8% females) treated for primary hypothyroidism. QOL was measured by the questionnaires Short-Form 36, Hospital Anxiety and Depression Scale and MFI20. Post hoc analysis was performed on the relation of QOL at baseline and BMI, thyroid hormones and other serum values. QOL in patients was also compared to the general population. Results: QOL was decreased compared to the general population. We found an inverse relationship between QOL and BMI. A relationship between QOL and serum thyroid parameters or auto-antibodies could not be found. Higher sex hormone binding globulin (SHBG) levels corresponded with a better QOL, which is explained by the negative association of SHBG with body weight and BMI. Conclusions: A decreased QOL in hypothyroid patients on thyroxine treatment is related to a higher body weight (BMI). Weight gain needs more attention in the treatment of hypothyroidism.