The objective was to examine the effects of traumatic brain injury (TBI), as compared with orthopedic injury (OI), relative to the risk for psychiatric disorder. There has only been one previous prospective study of this nature. Participants were age 7–17 years at the time of hospitalization for either TBI (complicated mild-to-severe) or OI. The study used a prospective, longitudinal, controlled design, with standardized psychiatric assessments conducted at baseline (reflecting pre-injury functioning) and 3 months post-injury. Assessments of pre-injury psychiatric, adaptive functioning, family adversity, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales. The outcome measure was the presence of a psychiatric disorder not present before the injury (“novel”), during the first 3 months after TBI. Enrolled participants (N=141) included children with TBI (N=75) and with OI (N=66). The analyses focused on 118 children (84%) (TBI: N=65; OI: N=53) who returned for follow-up assessment at 3 months. Novel psychiatric disorder (NPD) occurred significantly more frequently in the TBI (32/65; 49%) than the OI (7/53; 13%) group. This difference was not accounted for by pre-injury lifetime psychiatric status; pre-injury adaptive functioning; pre-injury family adversity, family psychiatric history, socioeconomic status, injury severity, or age at injury. Furthermore, none of these variables significantly discriminated between children with TBI who developed, versus those who did not develop, NPD. These findings suggest that children with complicated mild-to-severe TBI are at significantly higher risk than OI-controls for the development of NPD in the first 3 months after injury.