The direct and inferential mediation model proposes that reading comprehension is the result of relationships between prior knowledge, decoding, strategies, vocabulary, and inferential ability. The original model includes causal relationships, established when evidence of the direct effect of one of the components on another is found, and correlational relationships, proposed between some components when no causal evidence is found. The objective of this study is to adapt the model for Spanish speakers based on a systematic review. The causal relationships and the proposed correlations are supported by a single study or a meta-analysis, in both cases the effect size is significant. Causal relationships are also established when the effect size is not significant, but substantially important. Forty-three intervention studies are selected that support five causal relationships: from strategies, vocabulary and inferential ability to reading comprehension; and from prior knowledge and strategies to inferential ability. Seventy-four correlational studies that support seven correlations are also selected: between prior knowledge and reading comprehension; decoding and reading comprehension; strategies and prior knowledge; vocabulary and inferential ability; decoding and vocabulary; decoding and prior knowledge; and decoding and inferential ability. The effect sizes of the causal relationships are between g = 0.47 and g = 1.16, and the effect sizes of the correlations between r = .2 and r = .47.