Background: Studies have suggested that patients with prior gastric bypass may be at increased risk for hypocalcemia following thyroidectomy. Unfortunately, most of these studies are limited to case reports and small series. This study represents the largest sample size to date to assess the incidence of post-thyroidectomy hypocalcemia in patients with a history of bariatric surgery. Methods: The TriNetX Research Network was queried to retrospectively identify patients with prior bariatric surgery who underwent total thyroidectomy between 2011 and 2021. The incidence of hypocalcemia following surgery was compared with patients who underwent total thyroidectomy, and hemithyroidectomy with no history of bariatric surgery. Results: We identified 446 patients with a history of bariatric surgery and subsequent thyroidectomy, 29,346 patients with total thyroidectomy, and 19,603 patients with hemithyroidectomy alone. The one-month incidence of hypocalcemia was 54.7% in those with a history of bariatric surgery who underwent thyroidectomy, 43.9% in those with thyroidectomy alone (relative risk, RR = 1.2 [confidence interval, CI 1.1-1.4], p < 0.001), and 8.1% in those with hemithyroidectomy only (RR = 6.8 [CI 6.1-7.4], p < 0.001). Permanent hypocalcemia was documented in 11.4% of patients with prior bariatric surgery who underwent thyroidectomy, 7.7% of those with thyroidectomy only (RR = 1.5 [CI 1.1-1.9], p = 0.003), and 2.9% of patients with hemithyroidectomy alone (RR = 3.9 [CI 3.0-5.2], p < 0.001). Significant differences persisted after matching demographics, prior need for supplementation, and risk factors for hypocalcemia after thyroidectomy. When stratified by bariatric procedure, patients with a history of Roux-en-Y gastric bypass (RYGB) (n = 35) had a greater, although not statistically significant, risk of short-term hypocalcemia (51.4%; RR = 1.2 [CI 0.8-1.6], p = 0.37), and a significantly increased risk of permanent hypocalcemia (20.0%; RR = 2.6 [CI 1.3-5.1], p = 0.005) compared with thyroidectomy alone. Sleeve gastrectomy (SG) (n = 40) was not associated with an increased risk of short-term (40.0%; RR = 0.9 [CI 0.6-1.3], p = 0.62) or permanent (7.5%; RR = 1.0 [CI 0.3-2.9], p = 0.96) hypocalcemia. Conclusions: Prior RYGB, but not SG, may increase the risk of permanent hypocalcemia after thyroidectomy. Additional research is necessary to determine optimal prevention and treatment strategies to reduce morbidity in this population.