Kaposi sarcoma (KS) is a rare disease, and especially for classic KS, a gap exists in the literature about which chemotherapeutics should be given. Here we present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 patients with KS treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics of and the chemotherapeutic agents administered to the 16 patients with KS diagnosed in our center based on the medical records obtained. The median age, gender, KS type, involved site, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4-85.8 years). Among the patients, one had immunosuppression-related KS, four had acquired immune deficiency syndrome-related KS, and 11 had classic KS. Regarding the first-line cytotoxic therapy, seven patients received pegylated liposomal doxorubicin (PLD), six received paclitaxel, two received oral etoposide, and one received the doxorubicin, bleomycin, and vincristine regimen. The Kaplan-Meier analysis showed that the PFS was 39.9 months (95% confidence interval (CI), 7.7-72.0). In the first-line setting, a significant difference in PFS was observed between the PLD-and paclitaxel-treated groups (unreached vs. 12.8 months; p = 0.033). The OS was 66.1 months (95% CI, 30.2-102.0). The ORR and DCR of the 16 patients were 43.8%, and 81.3%, respectively. No grade 3 or 4 toxicity was observed. This retrospective study showed that among the most preferred chemotherapeutic agents, PLD seems better than paclitaxel in terms of PFS and response rates, and it showed a good safety profile in patients with KS.