As schools implement response to intervention to identify and serve students with learning difficulties, it is critical for educators to know how to evaluate screening measures. In the present study, Dynamic Indicators of Basic Early Literacy Skills Oral Reading Fluency was used to compare the differential decisions that might occur in screening accuracy when predicting two reading comprehension measures (i.e., Stanford Achievement Test–10th Edition and Gates-McGinitie Reading Test–Fourth Edition) at the end of second grade. The results showed that the Dynamic Indicators of Basic Early Literacy Skills Oral Reading Fluency tended to have higher sensitivity and negative predictive power for Stanford Achievement Test–10th Edition and higher specificity and positive predictive power for Gates-McGinitie Reading Test–Fourth Edition. Furthermore, attempting to achieve a criterion of positive predictive power for a given reading comprehension outcome (Stanford Achievement Test–10th Edition, in this study) appears to render a favorable balance compared to other indices of diagnostic accuracy. These results are discussed in light of trade-offs and a need for considering specific contexts of schools and districts.