Recent behavioural and brain imaging studies have provided evidence for rightward and leftward attention shifts while solving addition and subtraction problems respectively, suggesting that mental arithmetic makes use of mechanisms akin to those underlying spatial attention. However, this hypothesis mainly relies on correlative data and the causal relevance of spatial attention for mental arithmetic remains unclear. In order to test whether the mechanisms underlying spatial attention are necessary to perform arithmetic operations, we compared the performance of right brain-lesioned patients, with and without left unilateral neglect, and healthy controls in addition and subtraction of two-digit numbers. We predicted that patients with left unilateral neglect would be selectively impaired in the subtraction task while being unimpaired in the addition task. The results showed that neglect patients made more errors than the two other groups to subtract large numbers, whereas they were still able to solve large addition problems matched for difficulty and magnitude of the answer. This finding demonstrates a causal relationship between the ability to attend the left side of space and the solving of large subtraction problems. A plausible account is that attention shifts help localizing the position of the answer on a spatial continuum while subtracting large numbers.