High school chemistry teachers' experiences learning science through lectures and verification labs make it difficult for them to transition to inquiry-based approaches called for in the U.S. National Science Education Standards. Unfortunately, widely implemented approaches to teacher professional development (PD) aimed at reform, such as short-term workshops and fragmented courses, have not been effective. Target Inquiry (TI), a new model for high school chemistry teacher PD, attempts to incorporate research-driven features of PD into a coherent, rigorous, and in-depth program. TI has three core experiences delivered over 2.5 years which have been shown to positively affect teaching methods and student outcomes, including a chemistry research experience, inquiry materials adaptation, and action research. TI has been implemented and studied over the past 4 years with a demographically diverse teacher cohort to examine teacher and student outcomes of the model. The Reformed Teaching Observation Protocol (RTOP) was used to evaluate TI teacher instructional quality before, during, and after TI participation. A repeated-measures ANOVA yielded significant increases with high effect sizes in RTOP total (N = 6, p = 0.001, eta[superscript 2] = 0.80) and subscale scores over four years. Follow-up tests showed that it took two years of TI (including the research experience and materials adaptation) to produce detectable gains in scores. Qualitative data from teacher interviews and implementation journals described instructional changes that align with the quantitative results. These findings show that TI produces measurable improvements to teacher practice and promises to improve high school science instruction on a broader scale. (Contains 5 tables and 6 figures.)