Objective To evaluate the patterns and predictive factors of ipsilateral and contralateral central lymph node metastasis (CLNM) in the unilateral papillary thyroid carcinoma (PTC) patients with clinically node-negative neck (cN0). Methods We retrospectively reviewed the clinicopathological characteristics of 46 patients with cN0 unilateral PTC, including gender, age, multiplicity, tumor size, extrathyroidal extension, Hashimoto thyroiditis (HT), and T stage. Chi-square test and logistic regression were used to evaluate the patterns and predictive factors of ipsilateral and contralateral CLNM in cN0 unilateral PTC patients. Results Ipsilateral CLNM and contralateral CLNM were present in 32.6%(15/46) and 21.7% (10/46) of the patients, respectively. In patients with contralateral CLNM, 70.0% (7/10) had isolated contralateral CLNM without ipsilateral CLNM. Twenty patients of the 41 (48.8%) with T1/T2 stage had CLNM. Univariate analysis showed that tumor size >1 cm, age <45 years and absence of HT were associated with ipsilateral CLNM (P<0.05). None of the above clinicopathological characteristics was associated with contralateral CLNM. Multivariate analysis showed that tumor size >1 cm (OR=4.890, P=0.044) was the independent predictor of ipsilateral CLNM, and HT (OR=0.086, P=0.034) was a protective factor of ipsilateral CLNM. Multifocal cancer was an independent predictor of contralateral CLNM (OR=7.60, P=0.038). Compared with isolated ipsilateral CLNM, contralateral CLNM occured more often in patients with HT (P<0.05). Conclusion Ipsilateral CLNM is the most frequent in cN0 unilateral PTC patients and contralateral CLNM may independently occurr without ipsilateral CLNM. CLNM is frequent in patients at T1/T2 stage and prophylactic central lymph node dissection (PCND) is suggested for these patients. Ipsilateral PCND should be considered in patients with a tumor size >1 cm, while contralateral PCND may be more valuable for patients with multifocal cancer or HT.