Background: Human immunodeficiency virus (HIV) infection is associated with an increased risk of hypercoagulability and treatment with antiretroviral agents especially protease inhibitors has also been reported to contribute to this risk. Altered fibrinolytic activity is reported as a mechanism of increased thrombotic risk in HIV patients on therapy. However, this has not been investigated in our environment. Objective: To evaluate and compare PAI-1 levels as a marker of thrombotic risk in HIV-infected persons on PI-based HAART regimen with those on non-PI-based therapy and to correlate PAI-1 with haematological parameters. Methods: This was a comparative cross-sectional study conducted at the University of Calabar Teaching Hospital (UCTH), Calabar, Cross River State. A total of 125 subjects including 45 HIV-positive patients on PI-based HAART regimen, 42 HIV-positive patients on non-PI-based HAART regimen and 38 Controls. The controls include 18 HIV-positive therapy naïve patients and 20 HIV-negative controls. PAI 1 and blood counts were estimated using standard methods. Data were analyzed using the IBM version of the statistical package for social sciences (SPSS) version 22. Statistical significance was set at 0.05. Result: The median PAI-1 level was significantly increased in patients on PI-based HAART regimen (p  =  0.004). The blood counts did not differ significantly between patients on PI and non-PI-based HAART regimens (p > 0.05). There were no significant correlations between PAI-1 levels and blood counts (p > 0.05). Conclusion: PAI-1 level is elevated in HIV patients on PI-based HAART regimen. However, the association with thrombotic events could not be established in the study.