Study objective: To compare the effect of normal saline (NS), lactated Ringer's, and Plasmalyte on the acid-base status of dehydrated patients in the emergency department (ED). Method: We conducted a prospective, double-blind, randomized trial of consecutive adult patients who presented to the emergency department with moderate-severe dehydration. Patients were randomly allocated to blindly receive normal saline (NS), lactated Ringer's or Plasmalyte at 20 ml/kg/h for 2 hours. Outcome measures of the study were pH and changes in electrolytes, including serum potassium, sodium, chloride and bicarbonate levels at 0, 60, and 120 minutes in venous blood gas samples. Results: Ninety patients participated in the study and were randomized to NS (30 patients), lactated Ringer's (30 patients) and Plasmalyte (30 patients) groups. Mean age was 48±20 years and 50% (n=45) of the patients were female. All pH values were in the physiological range (7.35-7.45) throughout the study period. In the NS group there was a significant tendency to lower pH values, with pH values of 7.40, 7.37, and 7.36 at 0, 1, and 2 hours respectively. Average bicarbonate levels fell in the NS group (23.1, 22.2, and 21.5 mM/L) and increased in the Plasmalyte group (23.4, 23.9, and 24.4 mM/L) at 0, 1, and 2 hours, respectively. There were no significant changes in potassium, sodium, or chloride levels. Conclusions: NS, lactated Ringer's, and Plasmalyte have no significant effect on acid-base status and all can be used safely to treat dehydrated patients in the emergency department. However, NS can effect acidosis which might be significant in patients who have underlying metabolic disturbances; thus, its use should be weighed before fluid administration in the ED.