Background: Simple diffuse goiter (SDG) which is also known as endemic goiter usually occurs in a large number of certain populations. Serum thyroglobulin (TG) is a thyroid-specific glycoprotein, that serves as the source for thyroxine (T4) as well as triiodothyronine (T3) production within the lumen of thyroid follicles. Serum thyroglobulin and urinary iodine concentration are considered the most potent indicators of iodine status and thyroid functions as thyroid volume, thyroid nodularity, or iodine excretion have close associations to serum TG. Aim of the study: The aim of the study was to observe the association of serum thyroglobulin with different ages, gender, and grades of goiter in patients with simple diffuse goiter. Methods: This single-center observational study was conducted at the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka Bangladesh during the period from May 2014 to March 2016. The targeted sample size of this study was between 39 and 90 and the final sample size was determined as 87. A purposive sampling technique was used to select 87 patients with simple diffuse goiter attending the outpatient department of the study hospital. All data were processed, analyzed, and disseminated by using MS Office and SPSS programs as per necessity. Results: The lowest level of serum thyroglobulin (ng/mL) was found in the age group of 12-16 years (6.0±4.5 ng/mL) where the mean (±SD) age was 23.97±6.83 years. The mean (±SD) S. TG (ng/mL) levels in the male and female patients were 5.76 ± 5.72 and 11.60 ± 13.50 respectively. The mean (±SD) S. TG (ng/mL) levels among the grade I and II patients were 6.79±4.33 and 11.67±13.69 respectively. Overall, S. TG had no significant correlations with various factors like age gender, and goiter grades. According to the Pearson’s or Spearman analysis in assessing the correlations, with serum thyroglobulin levels, the P values were found 0.813, 0.294, and 0.319 against age, gender, and goiter grades. Conclusion: Serum thyroglobulin has not any statistically significant correlation with age, gender, or grades of goiter in patients with simple diffuse goiter.