Background: Clinical practice guidelines (CPGs) have the capacity to improve patient care and system performance. Targeted end users are more likely to implement CPGs judged to be of high quality and acceptable. Objectives: The objectives of this study were (1) to examine temporal trends in clinicians’ evaluations of, endorsements of, and their intentions to use CPGs and (2) to evaluate how clinician characteristics and clinician beliefs and attitudes are associated with these trends. Methods: The Program in Evidence-based Care (PEBC), a CPGs initiative of cancer system in Ontario, Canada, served as the study context. A retrospective analysis of CPGs evaluated between 1999 and 2005 by clinicians, the intended users, served as the data source for this study. Results: Between 1999 and 2005, 756 clinicians participated in the evaluation of 84 CPGs yielding 4091 survey responses. The 6-year mean scores ranged between 68.0% and 87.3% for the quality domain, 82.0% and 84% for the endorsement and intention to use ratings, respectively. The range in variance accounted for by practitioners was 23.8% to 38.3% for the quality domains, 25.5% in the endorsement item, and 18.7% in the intension to use. Over time, there were small but statistically significant gains in all ratings except the applicability score and for intention to use score where small declines were found (p’s < .05). CPG ratings were highest among clinicians who held the most favourable beliefs and attitudes about CPGs and lowest for those who had the least favourable beliefs and attitudes (p’s< .05). Those holding favourable beliefs and attitudes did not see a positive shift upwards on ratings as a function of time. In contrast, CPG ratings improved over time for clinicians whose beliefs and attitudes toward CPGs were unfavorable (p’s< .05). Conclusions: Ratings of the CPGs are strong and, for most domains, continued to improve over time. Continued engagement of clinicians who are least receptive to CPGs may be worth the effort; over time, these clinicians become more convinced of their value.