Objective: To determine the effect of consuming water with high fluoride content on thyroid hormone status. Method: The comparative cross-sectional study was conducted at Sammu Rind village of district Tharparkar, Pakistan, where ground water was the only source of drinking and had fluoride content >6-8mg/dL, and another set of people from Gadap Town, Karachi, where ground water had fluoride level of 0.3mg/L. Thyroid profile, including serum thyroid stimulating hormone, free triiodothyronine and free thyroxine, were checked for both the exposed and the unexposed groups, and data was cross-tabulated with thyroid profile to check statistical significance. Data was analysed using SPSS 20. Result: Of the 242 subjects, 121(50%) each were in the exposed and the unexposed group. Among the exposed, 15(12.4%) people had hypothyroidism, 104(86%) had euthyroid and 2(1.6%) had hyperthyroid. Corresponding values in the unexposed group were 10(8%), 105(87%) and 6(5%). The difference was not statistically significant (p>0.05).