Background: In this study, we investigated the associations Lake Urmia's drought to the prevalence of thyroid nodules (TNs) and metabolic syndrome (MetS) among local inhabitants of the lake. Methods: In this cross-sectional study which was started in 2014, we collected data on 992 adults who participated in the Azar cohort study, in Shabestar county, Iran. The sociodemographic status, smoking, and medical history of the subjects living in the areas adjacent to (n = 163) and far from (n = 829) Lake Urmia were collected through questionnaires. After obtaining written consent, anthropometric factors and blood pressure (BP) were measured. The lipid profile and fasting blood glucose (FBG) of the respondents were measured using colorimetric methods, and all underwent thyroid examination and sonography. Furthermore, the size and characteristics of nodules were determined with a fine-needle aspiration biopsy (FNAB) method. Results: We did not find any significant difference in the prevalence of TNs between the two groups (P=0.44), whereas the prevalence of MetS were significantly higher among the subjects from the regions that were far from the Lake (P=0.04). After adjustment for confounding factors (age and gender) in both groups, low risk of TNs (OR=1.20, 95% CI:0.89-1.62) and high risk of TNs (OR=1.19, 95% CI:0.65-2.19) were not significantly associated to MetS (P>0.05). Conclusion: In this study, Lake Urmia's drought was identified to be with no contribution to the prevalence of TNs and MetS. Therefore, long term perspective studies are suggested to reach precise results.