Acculturation has been linked to neuropsychological performance in several ethnic groups. However, research among Latina/o samples has examined primarily Mexicans/Mexican Americans and has not examined Latina/o clinical populations of Caribbean descent. This study examined associations between a multidimensional acculturation measure and neuropsychological performance among 82 HIV+ Caribbean Latina/o adults. Multivariate results showed that US acculturation significantly predicted 11-14% of the variance in global neuropsychological functioning, verbal fluency, and processing speed, whereas Latina/o acculturation predicted 6-8% of the variance in motor and executive function (trend level associations). Both linguistic and nonlinguistic cultural factors had distinct effects on neuropsychological performance.