This research investigated how word production is influenced by six feature-based semantic variables (number of semantic features, intercorrelational density, number of near semantic neighbors, semantic similarity, typicality, and distinctiveness). We simultaneously investigated effects of the six semantic variables on spoken picture naming in a large group of participants (n = 87), while controlling for other psycholinguistic variables. Across analyses, number of semantic features was the most consistent predictor with a facilitatory effect on naming latency and accuracy. In addition, inhibitory effects were found on naming accuracy for intercorrelational density and on naming latency for distinctiveness. The facilitatory effect of number of semantic features is suggested to stem from stronger semantic activation with an increasing number of semantic features, which results in facilitated selection of the word's lexical representation. In contrast, the inhibitory effect of intercorrelational density is most easily accounted for by increased competition at the lexical level. The mechanism underlying the inhibitory effect of distinctiveness is unclear. These findings indicate that future research on factors affecting word retrieval should also control for effects of number of semantic features, intercorrelational density, and distinctiveness. They also suggest that effects of the other semantic variables (e.g., semantic neighbors) reported in the literature were potentially overestimated due to insufficient control of other semantic and/or psycholinguistic variables.