Objectives. To evaluate the effectiveness and safety of acupressure on low back pain (LBP). Methods. We searched 7 electronic databases and 2 trial registries through December 28, 2020. Randomized controlled trials (RCTs) of acupressure on LBP were considered for meta-analysis with Revman 5.3 and Stata 15.0 software. Methodological quality was evaluated using the Cochrane Collaboration's tool. Trial sequential analysis (TSA) was used to quantify the statistical reliability. HETRED analysis and GRADE were used to determine the heterogeneity and quality of the results, respectively. Results. Twenty-three RCTs representing 2400 participants were included. Acupressure was superior to tuina massage on response rate (RR 1.25; 95% CI, 1.16 to 1.35; P<0.00001) and in the standardized mean difference (SMD) for pain reduction [SMD -1.92; 95% CI, -3.09 to -0.76; P=0.001]. Likewise, acupressure was superior to physical therapy [SMD, -0.88; 95% CI, -1.10 to -0.65; P<0.00001] and to usual care [SMD, -0.32; 95% CI, -0.61 to -0.02; P=0.04] in pain reduction. The Oswestry Disability Index was significantly improved by acupressure compared with usual care [SMD, -0.55; 95% CI, -0.84 to -0.25; P=0.0003]. The combination of acupressure with either manual acupuncture or electro-acupuncture showed significant improvements over the adjuvant therapies alone in response rate [RR 1.19; 95% CI, 1.13 to 1.26; P<0.00001], pain reduction, and the Japanese Orthopedic Association score (JOA). However, each study displayed substantial heterogeneity. Through subgroup sensitivity analysis and -HETRED analysis, the heterogeneity of acupressure compared with manual acupuncture decreased while the results maintained significance with respect to pain reduction [SMD -0.9; 95% CI, -1.21 to -0.6; P<0.00001] and JOA [SMD, 0.66; 95% CI, 0.33 to 0.98; P<0.00001]. Similar results were obtained comparing acupressure with electro-acupuncture with respect to pain [SMD, -1.07; 95% CI, -1.33 to -0.81; P<0.00001] and JOA [SMD, 0.89; 95% CI, 0.51 to 1.27, P<0.00001]. TSA demonstrated the effectiveness of acupressure as a standalone or as a combinative treatment (with manual acupuncture or electro-acupuncture) for LBP. Conclusion. Acupressure is an effective treatment for LBP. However, GRADE assessments downgraded the evidence in the trials, indicating that additional investigations are needed to confirm these observations. © 2021 Tao Li et al.