In this study, the pharmacokinetic parameters of the sustained‐release (SR) dosage form of clomipramine (CMI) were compared with those obtained after the administration of the immediate‐ release (IR) dosage form. Two studies were performed. In the first study, a single oral dose of both products was administered in 12 healthy volunteers, and in the second study, multiple doses of both products were administered in 6 patients with depression in which steady‐state plasma levels (Css) were determined. Plasma levels were assayed using an HPLC method. In the single‐dose study, the mean Cmax and AUC values of CMI were 63.37 ng/mL−1 and 1375.38 ng•h/mL−1 for the reference product and 32.55 ng/mL−1 and 1285.26 ng•h/mL−1 for the test product, respectively. The mean β and MRT values of CMI were 0.030 h−1 and 47.21 h for the reference product and 0.026 h−1 and 55.63 h for test product, respectively. Results showed that after the multiple‐dose study, the mean clomipramine plus demethylclomipramine values of Cssav were 406.2 ng/mL−1 for the reference and 328.6 ng/mL−1 for the sustained‐release dosage form. This product also presented less fluctuation in steady‐state plasma levels (1.08 vs. 1.23). The values of MRT and tmax were higher for the SR dosage form, showing that the drug was maintained longer in the body. The mean values for the ratio metabolite/drug were 2.06 and 2.41 for the IR and SR dosage forms, respectively. Neither AUC nor elimination half‐life was affected significantly after the administration of the sustained‐release dosage form.