Background: Cardiopulmonary resuscitation (CPR) is a technique or procedure that combined chest compression and rescue breathing to maintain enough circulation that prevents brain damage until other essential steps are taken to control the main cause of cardiac and respiratory arrest. The health care personnel should be qualified in the performing of cardiopulmonary resuscitation (CPR) to improve the survival rate of the victims. Therefore; it is necessary to use new methods for learning [1]. Objectives: the study aims to compare the effectiveness of self-instructional teaching strategy and traditional teaching approach on student’s knowledge toward cardiopulmonary resuscitation. Methods: A randomized comparative trial (RCT) design was carried out to compare the effectiveness between two teaching programs; a Traditional teaching method and a self-instructional approach on students’ knowledge concerning Cardiopulmonary Resuscitation in the College of Nursing/ University of Baghdad. A sixty student’s at the 2nd stage were randomly selected and then assigned into two groups (traditional teaching group and self-instructional group). A statistical package for social science (SPSS) program, version 24 was used for descriptive and inferential statistics. Results: study results indicated that both teaching methods (traditional teaching& self-instructional records high statistical significant differences (p =0.001).added to that the self- instructional strategy (16.9667+ 4.14) records significant differences in comparison with traditional teaching approach ( 11.76 + 4.040). Conclusions: based on the study results, the study concludes that both teaching methods improve student’s knowledge but the self- instructional strategy records higher student’s knowledge than traditional teaching.