Objective: A large goiter may cause compression of the trachea. The aim of this study was to investigate the impact of thyroidectomy on tracheal anatomy and airflow and to correlate this with changes in health-related quality of life (HRQoL) in patients with benign nodular goiter. Methods: Magnetic resonance images of the neck and respiratory flow-volume curves, including both inspiration and expiration, were performed prior to and 6 months following surgery. HRQoL was measured by selected scales from the thyroid-specific patient-reported outcome (ThyPRO). Cohen’s effect size (ES) was calculated as mean change divided by standard deviation at baseline. ES of 0.2–0.5 were defined as small, 0.5–0.8 as moderate, and values >0.8 as large. Results: Sixty-five patients completed all examinations. Median goiter volume was 58 mL (range, 14–642 mL) before surgery with surgical removal of a median of 43 g (range, 8–607 g). Six months after surgery, tracheal narrowing and deviation were diminished by a median of 26% (ES = 0.67, p < 0.001) and 33% (ES = 0.61, p < 0.001), respectively. Correspondingly, each 10% decrease in goiter volume resulted in 1.0% less tracheal narrowing (p < 0.001). Concomitantly, a small improvement was seen in forced inspiratory flow at 50% of forced vital capacity (ES = 0.32, p < 0.001). A reduction in tracheal narrowing was associated with improvements in the Impaired Daily Life scale (0.33 points per 1% decrease in tracheal narrowing, p = 0.03) of the ThyPRO questionnaire. Conclusions: In patients with symptomatic benign nodular goiter, thyroidectomy resulted in substantial improvements in tracheal anatomy and improvements in inspiratory flow, which were followed by gains in HRQoL. This information is pertinent when counseling patients before choice of treatment.