Intolerance of uncertainty (IU) is a risk factor for poor mental health. Acquired brain injury (ABI; for example, stroke, traumatic brain injury) often brings considerable uncertainty and increased mood disorder vulnerability. The Intolerance of Uncertainty Scale–Short Form (IUS-12) is a brief, well-validated IU measure in non-ABI samples, comprising two subscales, namely, Prospective Anxiety and Inhibitory Anxiety. Here, for the first time, we investigated its reliability and validity ( N = 118), and factor structure ( N = 176), in ABI. Both subscales had high test–retest reliability (intraclass correlation coefficients [ICCs] of .75 and .86) and were significantly associated with mood disorder symptoms. The two-factor model was superior to a one-factor IU model fit. Some fit statistics were less than optimal (standardized root mean square residual [SRMR] = 0.06, root mean square error of approximation [RMSEA] = 0.09); hence, exploration of other factor structures in other ABI samples may be warranted. Nonetheless, the IUS-12 appears suitable in ABI.