Difficulties in left–right discrimination (LRD) are commonly experienced in everyday life situations. Here we investigate the neurocognitive mechanisms of LRD and the specific role of left angular gyrus. Given that previous behavioral research reported women to be more susceptible to left–right confusion, the current study focuses particularly on the neural basis of sex differences in LRD while controlling for potential menstrual cycle effects (repeated measures design). 16 women and 15 men were presented pictures of pointing hands in various orientations (rotated versus non-rotated) and were asked to identify them as left or right hands. Results revealed that LRD was particularly associated with activation in inferior parietal regions, extending into the right angular gyrus. Irrespective of menstrual cycle phase, women, relative to men, recruited more prefrontal areas, suggesting higher top-down control in LRD. For the subset of rotated stimuli as compared to the non-rotated, we found leftward asymmetry for both men and women, although women scored significantly lower. We conclude that there are sex differences in the neurocognitive mechanisms underlying LRD. Although the angular gyrus is involved in LRD, several other parietal areas are at least as critical. Moreover, the hypothesis that more left–right confusion is due to more bilateral activation (in women) can be rejected.