Hyponatremia is the most frequently encountered electrolyte abnormality among hospitalized patients and thiazide users. In this large single-center retrospective study, we aim to determine the prevalence and risk factors of hyponatremia among patients at the King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia.To the best of our knowledge, this is the first such study in Saudi Arabia. A chart review was done for the years 2011-2012 of all admitted Saudi patients at KAMC who were treated with indapamide and hydrochlorothiazide. A total of 2000 patients were included [1237 females (629 indapamide and 608 hydrochlorothiazide) and 762 males (371 indapamide and 391 hydrochlorothiazide)]. Majority of the patients had type-2 diabetes mellitus (T2DM) with an overall prevalence of 72.2%. The overall prevalence of hyponatremia, regardless of severity, in the indapamide group was 37.3% versus 38.7% in the hydrochlorothiazide group. Stratification for age revealed that older patients had relatively higher levels of sodium (Na) as compared with younger patients, and this inverse association was significant (R = - 0.123; P <0.001). Increasing age, female gender and presence of T2DM were the significant risk factors for hyponatremia, explaining the 4.7% of the variance perceived (P <0.001). Our study suggests that the prevalence of hyponatremia among Saudi thiazide users is relatively high, and more so for the elderly and for those with T2DM. Early identification of this condition is important and caution should be exercised while prescribing thiazide drugs, particularly to those who are most at risk of developing hyponatremia to prevent related complications.