Background Adverse drug reactions as an ongoing public health issue, affects various aspects of society. This study aims to conduct a comprehensive study of usability and to evaluate usability of National Adverse Drug Reactions Reporting System. Methods This study was descriptive and cross-sectional. The National Adverse Drug Reactions Reporting System was evaluated based on the Pierotti heuristic evaluation checklist by seven experts. Every experts completed a heuristic evaluation checklist. The experts also measured the overall severity of each identified heuristic violation on a scale of 0 to 4, where 0 illustrates no problems and 4 illustrates a usability difficulties. Experts' views were extracted and the severity of each problem were analyzed and determined. Results A total of 265 problems were identified in the usability of this system. The severity of the problems that were identified according to the defined criteria were: severe problems 10 (3.9%), minor problems 135 (52.7%), Improvable but not necessary 120 (46.87%), and according to the evaluators major and technical problems were zero. The mean range of difficulty was between 1.03 and 8.56. The principle of “Flexibility and minimalist design " had the highest level of severity of the problem. Conclusion It is expected that the national adverse drug reaction reporting System will be reviewed again based on the needs of users, standards and changes included in the design. Also can help system designers to overcome its system usability problems.