Periodontal clinical trials rely on signs of gingival inflammation, periodontal probing methods, and intra-oral radiographic methods to measure outcomes of therapies that inhibit bone loss or foster bone gain. A single radiograph can provide information on the accumulation of past disease, and sequential radiographs can determine regeneration or progression of periodontal destruction. However, the precision achieved with a radiograph is associated with the actual exposure of the film and the subsequent analysis. A film exposed using standardized geometry and standardized processing has many advantages over non-standardized conventional film. If the patient population for a study is a small, selective group, or if one needs to identify the smallest amount of bone loss in the shortest time, standardized films may be used. Conversely, in a large-scale trial, the use of standardized films may prove to be impractical. Since the advent of personal computer-based image-processing workstations, digital-image analysis has also become a practical tool for clinical trials. Digital subtraction radiography is a highly precise and accurate technique for assessing bony changes associated with periodontal disease. Therefore, advanced digital-imaging systems may be more cost-effective in a clinical trial because the level of precision will have an effect on study length and sample size.