Aim Primary central nervous system lymphoma (PCNSL) is an aggressive, destructive, and rapidly progressive malignant brain tumor. Although aggressive therapies were studied trying to increase the median survival of PCNSL, the high relapse rate of PCNSL is still a big problem for the oncology medicine. A retrospective study was made to evaluate the efficacy and safety of pemetrexed in the treatment of patients with recurrent PCNSL. Methods Twenty-three confirmed recurrent PCNSL patients were selected during April 2012 and August 2016. Dexamethasone, B12, and folic acid were used to produce the toxicity related to pemetrexed. The patients were intravenously given pemetrexed (900 mg/m2) every three weeks for 6 weeks. Results After the treatment, 7 patients were in complete remission, 6 patients in partial remission, 4 patients in stable condition, and 6 patients in progression. There were 56.5% and 73.9% in the overall response rate and the disease control rate, respectively. The median overall survival (OS) was 6.6 months (95% CI, 4.6–8.6). Conclusion This study has been the first time to evaluate the safety and effectiveness of pemetrexed on elderly recurrent PCNSL patients. Results demonstrate that using high-dose pemetrexed might be a feasible and effective treatment for recurrent PCNSL in the elderly, and clinical trials should be conducted to further confirm it.