Objective The aim of the present study was to investigate the differences in quality of life (QOL) following complete or partial thyroidectomy and with regard to thyroid hormone replacement (LT4) therapy. Study Design Patients who underwent thyroidectomy were asked to complete the validated thyroid-specific ThyPRO QOL questionnaire at least 6 months following surgery. Setting Tertiary medical center. Methods Thyroid specific QOL questionnaire analysis. Results A total of 190 patients completed the ThyPRO questionnaire. Of them 89 patients had complete thyroidectomy and 101 patients had unilateral thyroid lobectomy. The total thyroidectomy group had significantly worse overall QOL self-assessment score than the lobectomy patients (p < 0.0001). Patients receiving LT4 therapy regardless of the extent of surgery, reported worse QOL compared to patients not receiving LT4. Conclusions Quality of life following thyroid surgery is significantly related to hypothyroidism and the requirement for LT4 therapy, rather to the extent of surgery. The best QOL was reported in patients treated with lobectomy who did not require LT4 therapy.