High definition transcranial direct current stimulation (HD-tDCS) targeting brain areas involved in pain processing has shown analgesic effects in some chronic pain conditions, but less modulatory effect on mechanical and thermal pain thresholds in asymptomatic subjects. This double-blinded study assessed the HD-tDCS effects on experimental pain and hyperalgesia maintained for several days in healthy participants. Hyperalgesia and pain were assessed during three consecutive days following provocation of experimental pain (nerve growth factor injected into the right-hand muscle) and daily HD-tDCS sessions (20-minutes). Forty subjects were randomly assigned to Active-tDCS targeting primary motor cortex and dorsolateral prefrontal cortex simultaneously or Sham-tDCS. Tactile and pressure pain sensitivity were assessed before and after each HD-tDCS session, as well as the experimentally-induced pain intensity scored on a numerical rating scale (NRS). Subjects were effectively blinded to the type of HD-tDCS protocol. The Active-tDCS did not significantly reduce the NGF-induced NRS pain score (3.5±2.4) compared to Sham-tDCS (3.9±2.0, P > .05) on day 3 and both groups showed similarly NGF-decreased pressure pain threshold in the right hand (P < .001). Comparing Active-tDCS with Sham-tDCS, the manifestation of pressure hyperalgesia was delayed on day 1, and an immediate (pre-HD-tDCS to post-HD-tDCS) reduction in pressure hyperalgesia was found across all days (P < .05). PERSPECTIVE: The non-significant differences between Active-tDCS and Sham-tDCS on experimental prolonged pain and hyperalgesia suggest that HD-tDCS has no effect on moderate persistent experimental pain. The intervention may still have a positive effect in more severe pain conditions, with increased intensity, more widespread distribution, or increased duration and/or involving stronger affective components.