Stoma creation has a great impact on patients' health related quality of life. Research aim: To assess the effect of health educational protocol on knowledge, practice and quality of life for two different age groups of colostomy patients. Research design: Quasi-experimental design (pre/post test) was utilized. Sample: Consisting of two different age patient groups with colostomy, the first age group represented middle – aged adults (20 - < 60), the second represented old adults (≥60). Setting: the study was conducted in Oncology Surgical Department and Outpatient Clinic of Oncology Institution at Sohag Hospital, Tools: three tools were utilized. Tool (I): Structured interview questionnaire included demographic & medical history assessment. Tool (II): knowledge & reported practice assessment for patients toward colostomy care. Tool (III): Stoma-Quality of Life Scale. Results: More than half of the patients in first age group (60.0%) had a good level of knowledge & reported practice post one month; while (72.0%) of patient in the second age group had a fair level with statistically significant difference P < 0.05 . Total quality of life mean score of the first age group was higher than second age group post, and follow-up of educational protocol application (74.33±8.14, & 72.47±5.44) compared with the second age group (72.8±9.63, & 70.04±5.65) with statistically significance difference P > 0.05. Furthermore a statistically significant correlation between QOL level and knowledge & reported practice level of patient in both age groups only post one month from protocol intervention (r = 0.123,0.546.) Conclusion: The educational protocol had positive effect on quality of life and increase knowledge & reported practice and for colostomy patients in two different age groups under the study. Recommendation: Studying the risk factors that affect the quality of life in two different age groups under study and the health outcomes of the colostomy patients