Background: The gold standard treatment for adolescent idiopathic scoliosis (AIS) is posterior spinal fusion (PSF). However, long-term consequences of PSF can include reduced spinal flexibility, back pain, and intervertebral disc degeneration. Vertebral body tethering (VBT) is a non-fusion alternative that preserves motion. We investigated the outcomes of VBT for the treatment of thoracolumbar (TL) major AIS in the largest single-surgeon series with a minimum 2-year follow-up (FU). Methods: We performed a retrospective single-center review. Inclusion criteria were AIS, Lenke 5/6 curvature, and skeletally immature Variables were compared using Student’s t-tests, Wilcoxon rank sum tests, Chi-square, and Fisher’s exact tests. Results: A total of 37 consecutive patients, age 14.1 ± 1.6 years, 86.5% F, 35.9 ± 11.5-month FU, were examined. Overall, 27 patients (73%) had Lenke 5 and 10 (27%) had Lenke 6 curvatures. Instrumentation of the TL curve alone was performed in 59.5%, and thoracic (T) and TL in 40.5% of patients. Overall, 45.9% of patients had two tethers placed in the TL spine; no patients had double tethers placed at the main thoracic curves. The TL (51 ± 8° to 20 ± 11°; p < 0.0001) and T (37 ± 13° to 17 ± 10°; p < 0.0001) curvatures improved from baseline to the latest FU. Overall, 89% of patients achieved major Cobb < 35°; the three patients who did not experienced at least one cord breakage or required PSF. T5-T12 kyphosis increased (p = 0.0401) and lumbar lordosis was maintained (p = 0.9236). Both the TL inclinometer (16 ± 4º to 4 ± 2°; p < 0.0001) and T (6 ± 4° to 4 ± 3°; p = 0.0036) measurements improved. There was a 49% tether breakage rate as follows: 60% for single-cord TL constructs and 35% for double cords (p = 0.0991). There was an 8.1% re-operation rate as follows: one conversion to T PSF and revision of the TL tether; one release of the T tether and revision of the TL tether; one screw revision for radiculopathy. One patient was re-admitted for poor pain control. Conclusions: Patients with TL major curvature treated with VBT experienced a high rate of clinically successful outcomes with maintenance of lumbar lordosis and relatively low complication rates at the latest FU.