(1) Background: High-energy injuries of the pelvic ring are rare. The wide application of iliosacral screw fixation of the posterior pelvic ring is relatively new. The aim of the present study was to evaluate the long-term quality of life. (2) Methods: All patients treated with an iliosacral screw for a posterior pelvic ring stabilization after high-energy trauma at a level 1 trauma center between 2005 and 2015 were included. Pelvic ring injuries were classified according to the Tile classification adapted by AO/ASIF. The clinical evaluation included the patient-oriented questionnaires surveys of the Majeed Score, Iowa Pelvic Score (IPS), Work Ability Index (WAI), SF-36, EQ5D-5L. (3) Results: A total of 84 patients were included with a median follow-up of 130.1 months (IQR 95.0–162.0 months). The median ISS was 22.5 (IQR 16.0–29.0), mean Majeed Score 83.32 (SD ± 19.26), IPS 77.88 (SD ± 13.96), WAI 32.71 (SD ± 11.31), SF-36 PF 71.25 (SD ± 29.61) and EQ5D-5L 0.83 (SD ± 0.21). There was a notably difference between uni- and bilateral pelvic fractures (p = 0.033) as well as a correlation with the ISS (p = 0.043) with inferior functional outcome measured by IPS. (4) Conclusions: Long-term follow-up of iliosacral screw fixation of unstable pelvic ring fractures showed a good quality of life and functional outcome with equal EQ5D-5L results and inferior SF-36 physical functioning compared to the German population.