Many words in English resemble one another in multiple ways. Words with similar spellings are referred to as "orthographic neighbors." The purpose of this within-subject experimental study was to examine the effect of orthographic neighbors on the spelling acquisition of second-grade students. In each of five sessions of a computer-based experiment, 71 participants were presented with two prime words and prompted to learn the spelling of seven novel words. The latter seven words were control words (no meaningful connection with the corresponding prime word) and neighbor words (words representing various types of connections with the corresponding prime word). Spelling tasks were administered twice: immediately after the experiment and two days later. The findings suggest that spelling acquisition depends on two critical factors: orthographic neighbor type and orthographic processing ability. Students' spelling acquisition was supported by analogizing rime neighbors (e.g., "rain/vain"). However, facilitative effects were not found for substitution neighbors (e.g., "rain/ruin") and transposition neighbors (e.g., "clam/calm"). Additionally, a student's level of orthographic processing was an important determinant of spelling acquisition; students with well-developed orthographic processing ability correctly learned the novel words regardless of the presence of rime neighbors. In contrast, acquiring spelling was far more difficult for students with less developed orthographic processing ability, but their spelling acquisition was strongly facilitated by the presence of rime neighbors. Implications of this research are (a) learners' orthographic processing skills should be considered when designing spelling instruction and (b) early elementary students need instructional support when making orthographic analogies for substitution and transposition neighbors.