Purpose We investigated the clinical significance of diffuse uptake in remaining thyroid after unilateral lobectomy for thyroid cancer. Methods A total of 144 thyroid cancer patients who underwent $^{18}F$-FDG PET/CT after lobectomy were enrolled in the present study. The PET/CT images were evaluated for the presence of diffuse $^{18}F$-FDG uptake with maximum SUV (SUVmax) >2.0 in the residual thyroid and placed into one of two groups: with diffuse uptake and without diffuse uptake group. Clinical, laboratory, and PET/CT parameters in both groups were compared. Correlations between SUVmax of thyroid and available parameters were analyzed. Results Forty-two of 144 patients (29.2%) had diffuse thyroid uptake (mean SUVmax: $3.2{pm}1.1$). All patients with diffuse uptake and 96 (94.1%) without diffuse uptake were receiving thyroxine therapy (P=0.09). Thyroid function tests showed that most patients were euthyroid status (78.6 vs. 85.3%, P=0.36). TgAb levels were significantly higher in patients with diffuse uptake ($338.0{pm}664.6$ vs. $57.3{pm}46.4$, P<0.0001). Mean attenuation values in the diffuse uptake group were significantly lower ($72.2{pm}15$. vs. $97.0{pm}16.0$, P<0.0001). An inverse correlation was found between SUVmax and mean attenuation values of residual thyroid in all patients (r=-0.57, P<0.0001) and subgroup with diffuse uptake (r=-0.31, P<0.05). Conclusion In this study, diffuse $^{18}F$-FDG uptake in the residual thyroid after unilateral lobectomy was a relatively frequent finding and may be associated with chronic thyroiditis. This uptake is not influenced by thyroid status or thyroxine therapy. The $^{18}F$-FDG uptake is inversely correlated with mean attenuation value of thyroid.