Background: The Response to Intervention (RTI) approach involves the use of a dynamic model built around the systematic documentation of students' response to research-based instructional interventions. Although there has been widespread implementation of RTI models for early intervention and in some cases, as a means to identify students with learning disabilities (LD), little has been published on teacher implementation of RTI in naturalistic school settings. Purpose: The purpose of this study was to examine the RTI implementation process in two culturally diverse, urban schools. The authors describe the process of large-scale RTI implementation through the lens of Systems Change Theory. Research Design: This study of RTI in a naturalistic setting used grounded theory research methods to provide an in-depth description and qualitative analysis of challenges and successes experienced by RTI teams and teachers in schools required by state mandate to implement RTI. Data collection included semi-structured interviews and observations with 30 participants in two urban schools. Transcripts of interviews and field notes of direct observations were analyzed inductively through a four-tiered interpretive coding process that moved from the most concrete to more abstract levels of interpretation. Conclusions: The present study highlights challenges related to changes in procedures for monitoring student responsiveness in an RTI system used for special education identification. The emergence of themes from observation and interview data revealed how professional development gaps, school personnel's assumptions about culturally and linguistically diverse (CLD) learners and families, and external pressures from district and state accountability systems affected RTI implementation across two schools. Our observations revealed confusion over the components for practice in RTI as well as a lack of understanding related to the purpose of RTI to potentially improve outcomes and reduce referrals to special education for CLD youth. The issues that emerged as barriers to implementation serve to identify the systemic change factors needed to support large-scale RTI implementation.