Tactile spatial acuity is enhanced in blindness, according to several studies, but the cause of this enhancement has been controversial. Two competing hypotheses are the tactile experience hypothesis (reliance on the sense of touch drives tactile-acuity enhancement) and the visual deprivation hypothesis (the absence of vision itself drives tactile-acuity enhancement). Here, we performed experiments to distinguish between these two hypotheses. We used force-controlled grating orientation tasks to compare the passive (finger stationary) tactile spatial acuity of 28 profoundly blind and 55 normally sighted humans on the index, middle, and ring fingers of each hand, and on the lips. The tactile experience hypothesis predicted that blind participants would outperform the sighted on the fingers, and that Braille reading would correlate with tactile acuity. The visual deprivation hypothesis predicted that blind participants would outperform the sighted on fingers and lips. Consistent with the tactile experience hypothesis, the blind significantly outperformed the sighted on all fingers, but not on the lips. Additionally, among blind participants, proficient Braille readers on their preferred reading index finger outperformed nonreaders. Finally, proficient Braille readers performed better with their preferred reading index finger than with the opposite index finger, and their acuity on the preferred reading finger correlated with their weekly reading time. These results clearly implicate reliance on the sense of touch as the trigger for tactile spatial acuity enhancement in the blind, and suggest the action of underlying experience-dependent neural mechanisms such as somatosensory and/or cross-modal cortical plasticity.