(1) Background: Acquired brain injury (ABI) or spinal cord injury (SCI) constitutes a severe life change for the entire family, often resulting in decreased quality of life (QoL) and increased caregiver burden. The objective of this study was to investigate the effectiveness of a family intervention in individuals with ABI or SCI and in their family members. (2) Methods: An RCT of a family intervention group (FIG) vs. a psychoeducational group (PEG) (ratio 1:1) was performed. The FIG received an eight-week manual-based family intervention, and the PEG received one psychoeducational session. Self-reported questionnaires on QoL with the Mental Component Summary (MCS) and on caregiver burden with the Caregiver Burden Scale (CBS) were the primary outcomes. The data analysis involved linear mixed-effects regression models. (3) Results: In total, 74 participants were allocated randomly to the FIG and 84 were allocated randomly to the PEG. The FIG had significantly larger improvements on the MCS and significantly larger reductions on the CBS at the two-month follow-up than participants in the PEG (mean differences of 5.64 points on the MCS and −0.26 points on the CBS). At the eight-month follow-up, the between-group difference remained significant (mean difference of 4.59 points) on the MCS, whereas that on the CBS was borderline significant (mean change of −0.14 points). (4) Conclusions: Family intervention was superior to psychoeducation, with larger improvements in QoL and larger reductions in caregiver burden.