Carboplatin-based combinations are established in platinum-sensitive recurrent ovarian cancer. To improve the therapeutic index, new platinum-based combinations are required. Pemetrexed is a multi-targeted antifolate inhibiting thymidylate synthase. The aim of this study was to determine the maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) and to characterize toxicities of the combination of pemetrexed (Pem) and carboplatin (Cb). A standard three-patient cohort dose escalation was performed starting at Cb AUC-5 and Pem 500 mg/m2. Patients with platinum-sensitive recurrent ovarian cancer were eligible. Two levels of Cb (AUC-5, 6) and five levels of Pem (500, 600, 700, 800, and 900 mg/m2) were evaluated. DLTs were based on cycle 1. Twenty patients were enrolled. The median age was 57.4 years (37.3–75.3) and the median platinum-free interval was 26.2 months (7.2–124.4). There was one DLT at dose level 3 in cycle one. No serious adverse events related to the study therapy were observed. The 20 patients completed 112 cycles of Cb (104 were planned) and 115 cycles of Pem (112 were planned). The maximum dose level of Cb AUC-6 and Pem 900 mg/m2 was well tolerated. Response rates in 19 patients were: CR: 63.2%; PR: 21.1%; SD; 5.3%, PD: 10.5%. The combination carboplatin and pemetrexed is safe and well tolerated. A multicenter phase-II trial is currently underway.