Peripheral neuropathy (PN) is a common neurological complication of HIV infection that has debilitating effects on quality of life. While there has been a comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART-naïve patients, similar evaluation in ART-experienced patients is limited. This study investigated the prevalence and RFs for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy studies. Between February 2000 and June 2007, 522 ART-experienced participants who experienced virologic failure with a prior regimen and started new regimens were followed longitudinally and annually screened for signs and symptoms of PN. Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %, respectively. Aging, taller height, protease inhibitor use, and female sex were significant RFs for PN/SPN. The use of statin drugs was significantly associated with lower odds of SPN, and it may prevent progression from no SPN to SPN.