Background: Two studies were conducted to improve the development, reporting, and evaluation of practice guidelines. Objectives: Study 1 assessed the performance and usefulness of the Modified AGREE (M-AGREE) Instrument and a generic rating scale (GRS). Study 2 assessed the validity of the beta version of the AGREE II Instrument (B-AGREE II). Methods: Study 1 involved 156 participants (clinicians, developers/researchers, policy makers) who read a practice guideline, assessed it with either the M-AGREE and GRS (condition 1) or the GRS alone (condition 2), and completed a series of questionnaires which evaluated the usefulness and feasibility of the instrument(s) and required improvements. Study 2 involved 30 participants being randomly assigned to one of two practice guideline packages and evaluated it with the B-AGREE II. Each package included purposefully designed high and low quality excerpts of practice guideline content; one quality version of each item reflected in each package. Participants completed an assessment survey of the B-AGREE II. Results: In Study 1, all M-AGREE items and GRS items were rated as useful by participants and no differences emerged as a function of user type. All M-AGREE domains, except editorial independence, predicted users’ endorsement of and intentions to use a guideline. The act of applying the M-AGREE did not influence GRS, endorsement or intention to use scores. In study 2, content designed to be of high quality was rated higher than content designed to be of low quality; in 18 of the 21 items, the differences were statistically significant. The User’s Manual was rated by participants as appropriate, easy to use, and able to assist in differentiating good quality practice guidelines from poor quality practice guidelines. Conclusions: The results of these studies led to the final version of the AGREE II, a new international standard in guideline development, reporting, and evaluation.