Objective: The aim of this study was to investigate the association of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and osteonecrosis of the femoral head (ONFH). Methods: The pooled relative risk ratio (RR) and 95% confidence intervals (95% CI) were calculated using the the RevMan 5.0 software. Results: The present study included 969 patients with ONFH and 419 healthy controls. The Meta analysis results showed: There is association between PAI-1 gene 4G/5G polymorphism and the increasing risk of ONFH (allele model: RR = 1.24, 95% CI = 1.16 similar to 1.33; dominant genetic model: RR = 1.12, 95% CI = 1.05 similar to 1.18). It was found that the association between PAI-1 gene 4 G/5 G polymorphism and the susceptibility of ONFH (P < 0.05) through the comparison of Caucasian population and Asian people according to the analysis of different races. Conclusions: There is association between PAI-1 gene 4 G/5 G polymorphism and the increasing of the susceptibility of ONFH.