Background and Objective: Adequate fluid removal may decrease the mechanical ventilation time in intensive care. Ethacrynic acid as diuretic required comparatively in fewer dose than furosemide. The objective of the study was to compare the efficacy and safety of ethacrynic acid with furosemide in fluid overload patients associated with cardiac intensive care. Materials and Methods: A total of 248 patients with signs of volume overload in the cardiac intensive care unit were subjected to randomize. Patients were received 0.8 mg kg(-1) h(-1) of furosemide (FR group, n = 124) or 0.5 mg kg(-1) h(-1) ethacrynic acid (EA group, n = 124) at 1 mL h(-1), for maximum 3 days. Serum creatinine, urine output, body weight loss, cost of interventions and treatment-emergent adverse effects were evaluated. The Chi-square for independence or one-way ANOVA was performed at 95% of confidence level. Results: Furosemide and ethacrynic acid, both decreased serum creatinine and increased urine output. Patients of FR group had high weight loss than EA group at the time of discharge (p<0.0001). Hypocalcemia and hypomagnesemia had been reported in FR group and tinnitus and hearing loss had been reported in EA group during the follow-up period. Ethacrynic acid treatment was highly expensive treatment than frusemide (p<0.0001). Conclusion: Ethacrynic acid is safe and effective but costly alternative of frusemide.