© 2020 Taylor & Francis Group, LLC.Background/aim: The effect of isotretinoin on soluble VEGFRs has not been previously investigated. This study evaluate the effects of isotretinoin (13-cis-retinoic acid) on soluble VEGFR1 (sVEGFR1), soluble VEGFR2 (sVEGFR2) and soluble VEGFR3 (sVEGFR3). Methods: The study included 38 patients (28 females, 10 males) receiving systemic isotretinoin treatment and 38 healthy individuals (28 females, 10 males) with similar age and gender characteristics. The blood samples of the patient group at third months and blood samples of the control group were compared in terms of sVEGFR1, sVEGFR2 and sVEGFR3 concentrations. Results: It was significant that sVEGFR1 was low and sVEGFR3 was high in patients receiving isotretinoin (p:.038, p:.021, respectively). There was no significant change in sVEGFR2 levels between the groups (p:.519). Conclusions: We think that the effect of isotretinoin on sVEGFR1, sVEGFR2 and sVEGFR3 may be secondary to its effects on the VEGF family. However, after clarifying the effect of isotretinoin on the VEGF family, we think that it can be used in some tumors and vascular diseases.