There is a lack of consensus as to whether the laterality of central venous chest port (port) placement is a risk factor for port complications. This is partly because confounding variables were suboptimally controlled in prior studies. The purpose of this study is to retrospectively compare the port-related complication rate between right-sided and left-sided ports placed in oncologic patients using propensity score matching. A total of 3,126 consecutive adult (≥18 years old) oncologic patients (male/female: 1,571/1,555, median age: 62) who had a port placed between 2013 and 2021 were included in this study. Patients with port complications (infectious, mechanical, thrombotic, and skin complications) were identified through chart review. Propensity score matching generated a cohort of 277 pairs of patients for the right-sided and left-sided port groups that are balanced across 11 potentially confounding variables. The overall complication rate of each group was compared using Poisson regression. Multivariate proportional subdistribution hazard regression (PSHREG) analysis was also conducted to determine if port laterality is an independent risk factor for overall port complications. The cumulative follow-up period for the matched cohorts was 259,250 catheter-days (median per patient: 311 catheter-days, range:10–2,879 catheter-days). In the left-sided port group, a total of 59 ports (21.3%) were found to be associated with complications (36 infectious, 7 mechanical, 11 thrombotic, 12 skin-related), while 31 ports in the right-side port group (11.2%, P = 0.0013) were associated with complications (13 infections, 3 mechanical, 8 thrombotic, 8 skin-related), accounting for complication rates of 0.46 and 0.24 complications/1000 catheter-days, respectively (P = 0.0022). PSHREG analysis of the matched cohort further demonstrated laterality of port as an independent risk factor for port complication (hazard ratio = 2.015, 95% confidence interval = 1.306-3.108, P = 0.0015). Left-sided ports were associated with a higher risk of port complications when compared with right-sided ports in adult oncological patients based on propensity score matching analysis. The right-sided port placement is recommended to minimize the risk of port complications.