Background: Approximately 32% of all lymphoma patients experience immunocompromised severe avoidable side effects of nadir at home after discharge postchemotherapy. The certified oncology nurses employed at a large metropolitan hospital in Atlanta, Georgia, lack standardized discharge guidelines that include regulatory organizations’ recommendations to assist patients/families with at-home self-management of the avoidable side effects. Purpose: The purpose of this quality improvement project was to utilize the institution’s existing postchemotherapy discharge protocol to assess certified oncology nurses’ knowledge of severe avoidable side effects of nadir; modify the existing healthcare institution’s postchemotherapy discharge protocol to reflect standardized practice for promoting clinical practice continuity by leading organizations; conduct multifaceted training seminars to disseminate the modified postchemotherapy discharge guideline; evaluate the oncology nurses’ knowledge of severe avoidable side effects of nadir postchemotherapy after modified guideline implementation; and collaborate with the intraprofessional team to determine if the modified postchemotherapy discharge guideline was feasible and acceptable for system wide hospital implementation. Theoretical Framework: The theoretical framework used was Benner’s model of nurse proficiency: expert nurses develop skills and understanding of patient care through a sound educational base and a multitude of experiences. Methods: The existing postchemotherapy discharge protocol was used to develop a developed standardized guideline incorporating regulatory organizations’ recommendations for severe avoidable side effects of nadir postchemotherapy for nursing discharge information and patients’ at-home management. Ten oncology registered nurses on a 16-bed oncology unit participated in two 10-question Likert scale questionnaires based on the existing guideline (pretest) and the modified guideline (posttest) before and after an educational intervention. A quantitative nonparametric descriptive design was used. The questionnaires were analyzed with a two-tailed paired t test, p = 0.05, CI = 95, SD = 12. Results: Nurses significantly improved from pretest to posttest—63% before receiving modified guideline education and 83% after receiving education (p < 0.005). Conclusion: A standardized guideline that included regulatory organizations’ recommendations for at-home management of severe avoidable side effects of nadir showed significant nurses’ improvement in knowledge and competency. The effectiveness of nurses disseminating discharge information was paramount when knowledge awareness and appropriate patient/family assessment were incorporated in the discharge instructions.