There are few tried and tested mobile technology applications to enhance and standardize the quality of health care by frontline rural health providers in low-resource settings. We developed a media-rich, mobile phone-based clinical guidance system for management of fevers, diarrhoeas and respiratory problems by rural health providers. Using a randomized control design, we field tested this application with 16 rural health providers and 128 patients at two rural/tribal sites in Tamil Nadu, Southern India. Protocol compliance for both groups, phone usability, acceptability and patient feedback for the experimental group were evaluated. Linear mixed-model analyses showed statistically significant improvements in protocol compliance in the experimental group. Usability and acceptability among patients and rural health providers were very high. Our results indicate that mobile phone-based, media-rich procedural guidance applications have significant potential for achieving consistently standardized quality of care by diverse frontline rural health providers, with patient acceptance.