The purpose of this network meta-analysis was to investigate the efficacy and safety of total knee arthroplasty (TKA) considering seven different surgical approaches. Four databases (PubMed, Cochrane Library, EMBASE, Web of Science) were searched for clinical randomized controlled trials (RCTs) involving TKA with different surgical approaches. STATA 14.0 was used to construct network maps and publication bias graphs and conduct inconsistency tests, network meta-analyses, and surface under the cumulative ranking (SUCRA) calculations. A total of 51 RCTs involving 4061 patients and 4179 knees from 18 countries were included. Among the seven surgical approaches, the midvastus approach (MV) was the top choice to reduce tourniquet use time, the subvastus approach (SV) had the shortest operation time, the mini-midvastus approach (Mini-SV) was associated with the least amount of time to achieve straight leg raise (SLR) after surgery, the mini-medial parapatellar approach (Mini-MP) reduced postoperative pain effects, and the medial parapatellar approach (MP) was the best approach to improve range of motion (ROM). Excluding the quadriceps-sparing approach (QS), which was not compared, the use of the mini-midvastus (Mini-MV) may shorten the hospital stay. There were no significant differences in blood loss, postoperative complications, American Knee Society Score (AKSS) objective, or AKSS functional between the seven surgical approaches (P > 0.05).