Orthopedic specialty hospitals may allow for more streamlined and efficient care, resulting in shorter lengths of stay, lower costs, and fewer complications. Surgical site infection can be a devastating complication of orthopedic procedures and is difficult to treat successfully, requiring substantial cost and resources. The goal of this study was to determine whether specialty hospitals had lower rates of infection than tertiary care institutions. Records were reviewed for patients undergoing primary total hip, knee, or shoulder arthroplasty and single-level lumbar fusion from 2010 to 2017 at 2 academic tertiary hospitals and 2 specialty hospitals. Patient demographic information, comorbidities, and the development of deep surgical site infection within 1 year of the index procedure were recorded and compared between the groups. Multivariate analysis identified variables that significantly correlated with infection rates. A total of 20,264 patients (73.9%) underwent surgery at a tertiary hospital, and 7169 (26.1%) underwent a procedure at a specialty hospital. Patients treated at orthopedic specialty hospitals had lower rates of infection at 1 year (0.6% vs 0.2%, P<.0001). Of the infections, 42 (32.3%) occurred in the knee, 50 (38.5%) in the hip, 24 (18.5%) in the spine, and 12 (10.8%) in the shoulder. When controlling for a healthier patient population, procedures performed at specialty hospitals were an independent predictor of infection within 1 year (odds ratio, 0.3693; P=.0012). Although tertiary hospitals care for older patients with more medical comorbidities, patients undergoing orthopedic procedures at a specialty hospital may be at lower risk for infection. Further study is needed to identify the processes associated with reduced infection rates and to determine whether they can be adopted at tertiary centers. [Orthopedics. 2021;44(4):e521-e526.].