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OBJECTIVE: To assess the effect of truncal ligation of the inferior thyroid artery in comparison with ligation of secondary branches as a risk factor for postoperative hypocalcemia. DATA SOURCES: A search was conducted using the Medical Subject Headings and free-text terms "thyroid*" and "truncal ligation*" in PubMed Central, PubMed, Embase, and Latin American and Caribbean Health Sciences Literature databases for trials published between January 1985 and October 2016. A Google search with the same terms, and a "snowball" approach was designed to retrieve the largest number of articles. REVIEW METHODS: Controlled trials (randomized or not) of adults who underwent total/bilateral subtotal thyroidectomy were searched, and truncal ligation versus nontruncal ligation of the inferior thyroid artery was compared. Data were acquired following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality of randomized controlled trials was assessed in accordance with Cochrane Collaboration guidelines, and for nonrandomized controlled trials, the Newcastle-Ottawa quality assessment scale for cohort studies was used. Pooled results are presented as risk differences with a random effects model. The main outcome was postoperative temporary and definitive hypocalcemia. RESULTS: We found 11 nonrandomized controlled trials and nine randomized controlled trials with 1940 patients: 977 patients in the trunk ligation group and 963 patients in the nontruncal ligation group. The risk difference for biochemical hypocalcemia was 6% (95% confidence interval [CI]: 2% to 11%), for symptomatic hypocalcemia 6% (95% CI: 1% to 10%), and definitive hypocalcemia 0% (95% CI: -1% to 1%) in the whole group. CONCLUSIONS: Truncal ligation of the inferior thyroid artery increases the risk of temporary and symptomatic hypocalcemia but not the risk of definitive hypocalcemia. Laryngoscope, 128:534-541, 2018.