Some studies suggest that increased homocysteine in blood leads to alterations in coagulation and fibrinolysis; however, the precise mechanism is not clear. The aim of this study was to compare different concentrations of homocysteine and aspirin on fibrinolysis in the plasma of healthy individuals in vitro. Different concentrations of homocysteine (200, 100, and 50 μmol/l) and aspirin (100, 10, and 1 mg/l) were added to the healthy people plasma citrate. They were incubated at 37°C for 24 h. Then, fibrinolysis parameters were analyzed by the turbidimetric procedure at 405 nm. The independent-samples t-test was utilized to compare them (P < 0.05). Findings revealed that homocysteine at 200 μmol/l with aspirin 100 ml/g had significant changes in the lysis maximum velocity (0.150 ± 0.002), half-lysis time (218 ± 5.77), the total lysis time (446 ± 5.77), and lag time in lysis (119 ± 3.60), compared to homocysteine at 200 μmol/l lysis maximum velocity (0.110 ± 0.002), half-lysis time (278 ± 7.63), the total lysis time (515 ± 14.29), and lag time in lysis (176 ± 3.60), respectively (P < 0.05). Homocysteine at 200 μmol/l with aspirin 1 ml/g did not significantly change in either parameter (P > 0.05). Homocysteine at 50 μmol/l with aspirin (100, 10, and 1 mg/l) had significant changes in all fibrinolysis parameters (P < 0.05), compared to homocysteine at 50 μmol/l. The other concentrations were compared in the same way. Aspirin (more than 1 mg/l) had more effect on higher concentrations of homocysteine. Aspirin increased velocity of clot lysis and decreased lysis time of clot in the presence of homocysteine.