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Abstract Visual word recognition is facilitated by the presence oforthographic neighborsthat mismatch the target word by a single letter substitution. However, researchers typically do not considerwhereneighbors mismatch the target. In light of evidence that some letter positions are more informative than others, we investigate whether the influence of orthographic neighbors differs across letter positions. To do so, we quantify the number ofenemiesat each letter position (how many neighbors mismatch the target word at that position). Analyses of reaction time data from a visual word naming task indicate that the influence of enemies differs across letter positions, with the negative impacts of enemies being most pronounced at letter positions where readers have low prior uncertainty about which letters they will encounter (i.e., positions with low entropy). To understand the computational mechanisms that give rise to such positional entropy effects, we introduce a new computational model, VOISeR (Visual Orthographic Input Serial Reader), which receives orthographic inputs in parallel and produces an over‐time sequence of phonemes as output. VOISeR produces a similar pattern of results as in the human data, suggesting that positional entropy effects may emerge even when letters are not sampled serially. Finally, we demonstrate that these effects also emerge in human subjects' data from a lexical decision task, illustrating the generalizability of positional entropy effects across visual word recognition paradigms. Taken together, such work suggests that research into orthographic neighbor effects in visual word recognition should also consider differences between letter positions.