Background: Many scholars have espoused the use of culturally responsive instruction (CRI) for closing achievement gaps, yet there is a paucity of research supporting its effectiveness. In this article, we share results of a mixed methods study that examined the use of the Culturally Responsive Instruction Observation Protocol (CRIOP) as a framework for teacher professional development. The CRIOP is a comprehensive model and evaluation tool that operationalizes culturally responsive instruction around seven elements: Classroom Relationships, Family Collaboration; Assessment; Curriculum/Planned Experiences; Instruction/Pedagogy; Discourse/Instructional Conversation; and Sociopolitical Consciousness/Diverse Perspectives. Focus of Study: This study was designed to answer the following questions: (1) Do teachers increase their use of culturally responsive practices as they participate in CRIOP professional development? (2) What is the relationship between implementation of culturally responsive instruction and student achievement in reading and mathematics?, and (3) What are teachers' perceptions of their successes and challenges in implementing culturally responsive instruction? Participants: Twenty-seven elementary teachers participated in this study. Of the 27 participants, all were female, 26 were White, and all were native speakers of English. Student achievement data were collected from students enrolled in classrooms of participating teachers at the two schools in the study that administered the Measures of Academic Progress (MAP) test. Of the 456 students who were participants, 397 (87.3%) received free or reduced lunch, and 128 (28% of total sample) were classified as English Language Learners (ELLs). Intervention: Three training sessions were held before school began and during the fall semester. Additionally, throughout the school year teachers received individual classroom coaching, on-site professional development, and instructional planning support. Participating teachers received an average of 50.4 hours of classroom-based coaching and mentoring during the intervention, which included observations, meetings with individual teachers and teacher teams, curriculum planning sessions, and collaborative creation of individualized action plans. The CRIOP was used as a professional development framework. The intended outcome of on-site support was to increase the incorporation of culturally responsive instruction in teachers' daily practices, resulting in more culturally responsive classroom relationships, assessment and instructional practices, and use of discourse. Research Design: This study utilized a concurrent triangulation mixed methods design. Data sources included classroom observations, student achievement results, and post observation teacher interviews. The CRIOP instrument was used for classroom observations to determine the extent of implementation of culturally responsive practices. Following each classroom observation, field researchers conducted an audio-recorded semistructured interview using the CRIOP Post-Observation Teacher Interview Protocol and The CRIOP Family Collaboration Teacher Interview Protocol. These protocols were designed to elicit additional information that might not have been readily apparent from data gleaned during the observation. In addition, participants were interviewed to determine their perceptions of culturally responsive instruction. Three interview questions and responses were transcribed and coded for analysis: How do you define culturally responsive instruction? What are your biggest successes with using Culturally Responsive Instruction with your students? What are your biggest challenges with using Culturally Responsive Instruction with your students? Integration of quantitative and qualitative data occurred during data collection and interpretation. Findings: Results of classroom observations showed that teachers had significantly higher levels of CRI implementation in the spring compared to fall. Data on student achievement indicated that students of high implementers of the CRIOP had significantly higher achievement scores in reading and mathematics than students of low implementers. The results of this study also suggest that teachers face several challenges in implementing CRI, including constraints imposed by administrators, high-stakes accountability, language barriers in communicating with families, and the sheer complexity of culturally responsive instruction. Conclusions/Recommendations: Although numerous scholars have espoused the value of culturally responsive instruction (CRI), there is limited research on its effectiveness. The results of this investigation suggest that the CRIOP shows promise both as a framework for teacher professional development and as an observation instrument in investigations of culturally responsive instruction. Findings also indicate that one of the biggest challenges in implementing CRI is its multidimensionality in that it includes several components (e.g., student relationships, family collaboration, assessment practices, instructional practices, discourse practices, and sociopolitical consciousness), which together comprise the CRIOP model. Future research including an experimental design is needed to determine the effectiveness of the CRIOP as a measure of culturally responsive instruction and as a framework for intervention.