BACKGROUND The characteristics of multifocal PTC remain controversial. Surgical approach to multifocal tumor changes between centers. This study aimed to evaluate the incidence of bilateral involvement, predictive factors for bilaterality and whether bilaterality was related with more aggressive histopathologic features or prognosis in patients with multifocal PTC. METHODS Medical records and pathologic data of 914 patients who underwent total thyroidectomy and diagnosed with PTC were retrospectively reviewed. The patients with multifocal disease were detected and divided into two subgroups as unilateral-multifocal PTCs and bilateral multifocal PTCs. Those two groups were compared regarding to demographic, clinical and histopathological features. RESULTS Multifocal disease was detected in 294 patients (32.7%). Of all, 102 patients (36.7%) had unilateral whereas 192 cases (65.3%) had bilateral involvement. As a result of univariate analysis, bilaterality was significantly associated with the number of tumor foci (p < 0.001), tumor size (p = 0.008), TSH (p = 0.002) and capsule invasion (p = 0.018). Multivariate analysis demonstrated that the number of tumor foci and TSH level were independent risk factors for bilaterality in multifocal PTC (p < 0.001 and p = 0.006, respectively). Bilateral and unilateral tumors had similar local/regional and distant recurrence rates. CONCLUSIONS Incidence of bilateral tumors is high and increases with the number of tumor foci in multifocal PTC. Bilateral involvement in multifocal PTC is not associated with worse prognosis.TSH can be taken as a preoperative indicator able to predict multifocal cancers and guide clinical decision making and surgical management.