Methods: Eleven patients with shoulder infection were treated by two-stage RTSA following temporary antibiotic-loaded cement spacer. Of the 11 shoulders, nine had pyogenic arthritis combined with complex conditions such as recurrent infection, extensive osteomyelitis, osteoarthritis, or massive rotator cuff tear and two had periprosthetic joint infection (PJI). The mean follow-up period was 29.9 months (range, 12–48 months) after RTSA. Clinical and radiographic outcomes were evaluated using the visual analog scale (VAS) score for pain, American Shoulder and Elbow Surgeons (ASES) score, subjective shoulder value (SSV), and serial plain radiographs. Results: The mean time from antibiotic-loaded cement spacer to RTSA was 9.2 months (range, 1–35 months). All patients had no clinical and radiographic signs of recurrent infection at final follow-up. The mean final VAS score, ASES score, and SSV were significantly improved from 4.5, 38.6, and 29.1% before RTSA to 1.7, 75.1, and 75.9% at final follow-up, respectively. The mean forward flexion, abduction, external rotation, and internal rotation were improved from 50.0°, 50.9°, 17.7°, and sacrum level before RTSA to 127.3°, 110.0°, 51.8°, and L2 level at final follow-up, respectively. Conclusions Two-stage RTSA with antibiotic-loaded cement spacer yields satisfactory short-term clinical and radiographic outcomes. In patients with pyogenic arthritis combined with complex conditions or PJI, two-stage RTSA with an antibiotic-loaded cement spacer would be a successful approach to eradicate infection and to improve function with pain relief.