Reverse-flow flaps are preferable in reconstructive surgery due to their several advantages. However, they may have venous insufficiency and poor blood flow. In this study, effects of various pharmacological agents on the viability of reverse-flow flaps were investigated. Forty Sprague-Dawley rats were used. Superficial epigastric artery- and superficial epigastric vein-based reverse-flow island flaps were preferred. The rats were divided into 4 groups. Group 1 was considered as the control group. Group 2 was given verapamil 0.3 mg/kg per day, group 3 nifedipine 0.5 mg/kg per day, and group 4 Daflon 80 mg/kg per day for 7 days. On day 7, viable flap areas were measured, angiography was performed, serum nitric oxide levels were evaluated, and histopathological examination was done.The mean flap viability rate was 67.59% (±13.12259) in group 1, 77.38% (±4.12506) in group 2, 74.57% (±3.44780) in group 3, and 85.39% (±4.36125) in group 4 (P = 0.001). The mean nitric oxide level was 31.66 μmol/dL (±2.42212) in group 1, 51.00 μmol/dL (±2.96648) in group 2, 34.00 μmol/dL (±2.96648) in group 3, and 47.66 μmol/dL (±2.80476) in group 4 (P = 0.001). On angiography, there were vessel dilations and convolutions in group 2; capillaries became noticeable, and anastomotic vessels extended toward the more distal part of the flaps in group 4. Histological examinations showed severe inflammation in group 3 and minimal inflammation and venous vasodilatation in group 2.Verapamil and Daflon in therapeutic doses significantly increased the viability of reverse-flow island flaps. However, nifedipine did not make a significant contribution to the flap viability. The results of this study will contribute to the literature about the hemodynamics of reverse-flow island flaps and guide further studies on the issue.