Background <p>Skin exposure of central venous (CV) ports is a rare but serious complication in patients undergoing outpatient chemotherapy. While nutritional and procedural factors have been implicated in wound complications, little is known about the specific risk factors for CV port skin exposure.</p> Methods <p>This retrospective observational study included 190 patients who underwent CV port implantation for outpatient chemotherapy between January 2020 and December 2023. After excluding 32 patients with missing data, 158 patients were analyzed and divided into two groups based on the presence or absence of skin exposure of the port. Clinical and procedural characteristics were compared, and multivariate logistic regression analysis was performed to identify independent risk factors.</p> Results <p>Among the 158 patients, 10 (6.3%) experienced skin exposure of the CV port. Compared with patients without exposure, those in the exposure group had significantly lower BMI (18.3 [17.2–21.3] vs. 21.1 [20.1–24.6], <i>p</i> = .044) and serum albumin levels (3.4 [3.1–3.8] g/dL vs. 4.1 [3.7–4.3] g/dL, <i>p</i> = .003). Male sex (<i>p</i> = .032) and left anterior chest placement (<i>p</i> = .023) were also significantly associated with exposure. Multivariate analysis identified male sex, hypoalbuminemia, and left-sided port placement as independent risk factors. ROC analysis showed that serum albumin (AUC = 0.826) had better predictive performance than BMI (AUC = 0.777).</p> Conclusions <p>Male sex, hypoalbuminemia, and left anterior chest placement were independently associated with CV port skin exposure in patients undergoing chemotherapy. These findings highlight the importance of pre-procedural nutritional assessment and individualized port placement strategies to reduce the risk of skin-related complications.</p>