Objective To explore the safety and efficacy of trans-lumbar-and-peritoneally joint (TLPJ) approach for laparoscopic dissection of large neoplasms from adrenal glands. Methods Sixty patients with diameters ≥ 6.0 cm adrenal neoplasms were recruited in this study. Of the participants, 30 were given transperitoneally laparoscopic adenectomy and 30 were given TLPJ approach. We compared the basic characteristics of the patients, as well as their conditions during and after operations. Results The two groups of patients had similar characteristics. No significant differences were found between the two approaches in terms of conversion to open surgery, estimated blood loss, transfusion, operating time, side injury, fluctuations of heart rate and blood pressure, and vascular accidents (\P>0.05), although slight, but not significant, advantages were shown in the TLPJ patients on starting food intake and physical activities. Similar results were also found in drainage volume, time to remove drainage, length of hospital stay, usage of analgesic, fever incidence, infection and intestinal obstruction etc (\P>0.05). Above all, no significant differences were found between the two groups in recurrence, metastasis and overall survival rates (\P>0.05). Conclusion Laparoscopic surgery with TLPJ approach, translumbar combined with entirely side peritoneum opened, is safe and efficient compared with the traditional transperitoneal approach for patients with large adrenal neoplasms.