Speed of processing training has been shown to improve cognitive functioning in normal older adults. A recent study demonstrated that middle-aged and older adults with HIV also improved on a measure of speed of processing and a measure of everyday functioning after such training. The primary objective was to examine what predicts the speed of processing training gains observed in the previous study. Participants were administered an extensive battery of demographic, psychosocial, and neuropsychological measures at baseline. They were randomized either to the speed of processing training group (n = 22) or to a no-contact control group (n = 24). Participants received approximately 10 hours of computerized speed of processing training. Predictors of training gains on the Useful Field of View (UFOV) Test and the Timed Instrumental Activities of Daily Living (TIADL) Test were examined through correlational analyses. In general, those who performed worse on the UFOV and TIADL at baseline demonstrated significantly more training gains. Also, higher HIV viral load, poorer medication adherence, a higher number of years diagnosed with HIV, and lower baseline scores on the Wisconsin Card Sorting Test (an executive functioning measure) were correlated with better TIADL training gains. TIADL performance improved in those with higher HIV viral load, poorer medication adherence, and poor executive functioning. Speed of processing training may be a way to improve everyday functioning and therefore quality of life in more medically and cognitively vulnerable adults with HIV. © 2014 American Association of Neuroscience Nurses.