Abstract: A significant portion of hospitals health care expenditure in Jordan is spent on laboratory testing. This study aimed to assess the validity of certain clinical practice guidelines (for common pediatric diseases) in a Children`s Hospital in North Jordan and to estimate the possible reduction in laboratory healthcare expenditure upon applying these guidelines. This prospective descriptive study included children admitted with common diagnoses. Necessary clinical and diagnostic data were analyzed. A panel of experts, guided by a set of selected practice guidelines, decided the appropriateness of the ordered laboratory investigations. Two hundred and seventy eight patients completed the study, 3,526 tests were performed and 47.8% of these were considered unjustified which accounted for 39% of the total laboratory expenditure. Chemistry tests were both the most frequent 60.2% and the most unjustified 63%. Justified tests tended to yield more abnormal results (p = 0.002). Local validity of international clinical practice guidelines was acceptable. Adherence to these guidelines regarding tests ordering may result into significant reduction of laboratory utilization and significant expenditure saving 39%. More studies are needed to identify other aspects of inappropriate laboratory utilization and to develop and validate community-based guidelines.