Objective To compared the drug diffusion and clinical effect of modified paramedian interlaminar (mPI) approach with transforaminal (TF) approach for steroid injection in the lumbar epidural space. Methods The 64 patients diagnosed with lumbar disc herniation, were divided into mPI group and TF group according to different needle paths, 32 patients in each group. After puncture to the epidural space, two groups of patients were given 2 ml contrast agents and were observed contrast agents distribution in the epidural space and nerve root. Then, two groups were given 2 ml mixture of compound betamethasone injection 1ml and normal saline. The distribution of contrast agent in the anterior epidural space, the vascular uptake and the nerve irritation of the patients in the operation were observed. Record the Numeric Rating Scale (NRS) and 5‑Point Likert Scale (Likert) between the two groups at the time points of before, 3 month after treatment and the effective rate of 3 months after treatment was compared between the two groups. Results In mPI group, the diffusion level of contrast agent in anterior epidural space (level 2 and 3) was greater than that in TF group (P<0.05). Cases of contrast agent diffusion grade 3 was greater than that of TF group (P<0.05). The cases of vascular up take of contrast agents and nerve irritation in the mPI group were lower than those values in the TF group (P<0.05). There was no statistical significance in NRS, Likert score and effective rate between two groups 3 months after treatment (P<0.05). Conclusions On the basis of the same clinical effect of the two groups, the mPI approach is more effective and safer for transfer drugs into the anterior epidural space than the TF approach.