This study discusses the construct of oral reading fluency and examines its relationship to reading comprehension among adult English-as-a-Second-Language (ESL) learners of four first language (L1) backgrounds. One hundred and forty-nine adult learners of English with Arabic, Japanese, Spanish and Chinese language backgrounds participated in this study. The participants read a short passage aloud and completed the reading comprehension section of the TOEFL (Test of English as a Foreign Language). Oral reading fluency was measured through four componential elements: oral reading rate (word per minute/wpm), accuracy (word correct/wc), efficiency (word correct per minute/wcpm), and prosody. Stepwise regression analyses showed variations across language groups regarding the role of oral reading fluency in ESL reading comprehension. For participants of Chinese and Japanese L1 backgrounds, prosody was the only significant predictor of English reading comprehension, which accounted for 18% and 32% of its variance respectively. Oral reading efficiency (wcpm) was the only significant predictor for Arabic ESL learners, which accounted for about 46% of variance in English reading comprehension. For participants of Spanish background, both accuracy (wc) and rate (wpm) were significant predictors and together they accounted for a total of 65% of the variance in English reading comprehension. The results are discussed in relation to the orthographic depth hypothesis and orthographic distance between first language and English.