1) Background: This study examines the impact of Synar policy adoption on youth commercial access to tobacco products in Mississippi, the South, and the remaining U.S. The principal focus on youth commercial access is complemented by analyses of Synar's impact on minors' non-commercial access to tobacco and tobacco use patterns. Mississippi has been especially aggressive in implementing Synar, as evidenced by its unusually low retailer violation rates (RVRs). Synar, a mandatory, enforceable regulation meant to limit youth's retail access to tobacco, was implemented nationwide in 1997. This study is governed by a combination of conceptual insights from a diffusion of health innovation perspective and structuration theory. (2) Methods: Repeated cross-sectional data from 1995 to 2011 from the CDC Youth Risk Behavior Survey are analyzed using a pre/post-implementation, quasi-experimental analytic strategy. Tobacco access and use in the pre-Synar era (1995)(1996)(1997) are compared with two post-Synar periods (1999-2005 and 2007-2011), thereby highlighting diffusion effects related to this policy innovation within Mississippi, the South, and the remaining U.S. (3) Results: Analyses of temporal trends reveal that Mississippi and other study regions effectively restricted commercial access to tobacco. Positive outcomes associated with Synar adoption were observed several years after initial implementation, thus supporting a diffusion of innovation perspective. However, results also reveal that Mississippi youth were more inclined than their counterparts elsewhere to gain access to tobacco through non-commercial means after Synar implementation, and that declines in tobacco use among Mississippi youth were less robust than those observed elsewhere. Such variegated effects are in line with expectations linked to structuration theory. (4) Conclusions: Synar policy implementation has been generally effective at deterring youth access to tobacco and, in many cases, has yielded declines in tobacco use. However, there is no evidence that especially aggressive retailer compliance checks in Mississippi have yielded distinctive benefits for youth in this state.