Purpose: This study aimed to evaluate the safety and feasibility of extending the flushing interval beyond 4 weeks in adult cancer patients with chemoports. Methods: A literature search was conducted in online databases covering studies published between 2000 and 2021. Four reviewers independently performed a quality assessment of the selected studies. Additionally, a single-center retrospective study was conducted, analyzing the medical records of cancer patients who had completed chemotherapy and continued periodic heparin flushing for port maintenance from January 2018 to December 2022. Results: An assessment of 12 studies using the Scottish Intercollegiate Guidelines Network (SIGN) tool indicated that extending heparin flushing intervals to 8 weeks is supported by Grade B evidence, while intervals beyond 12 weeks are supported by Grade C evidence. The retrospective study revealed no significant differences in occlusion or infection rates when extending flushing intervals to 12 weeks compared to the standard 4-week interval, with a cumulative complication incidence of 3.4%. Conclusion: Extending chemoport flushing intervals to up to three months in adult cancer patients is safe and feasible, with no increased risk of infection or occlusion. Further research is recommended to include larger sample sizes and to evaluate the potential applicability of these findings to pediatric patients.