Purpose: A phase I study was conducted to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the pegylated liposomal doxorubicin (PLD) and oxaliplatin combination in patients with advanced solid tumors. Patients and Methods: Forty-five patients with advanced-stage solid tumors received escalating doses of PLD 25–50 mg/m<sup>2</sup> as 60-min intravenous (i.v.) infusion and oxaliplatin 80–130 mg/m<sup>2</sup> as 2- to 4-hour i.v. infusion on day 1 every 3 weeks without growth factors. Results: MTD was defined at PLD 45 mg/m<sup>2</sup> and oxaliplatin 130 mg/m<sup>2</sup>. Eleven dose levels were evaluated and DLTs were grade 2–3 neutropenia resulting in treatment delays, grade 3 neurotoxicity and nausea/vomiting. A total of 187 cycles were administered with two episodes of febrile neutropenia and one toxic death due to sepsis. Two (4%) and 6 (13%) patients developed grade 4 and 3 neutropenia, respectively, 2 (4%) and 1 (2%) grade 4 and 3 thrombocytopenia, and 1 (2%) grade 4 anemia. The most common nonhematological toxicities were grade 2–3 nausea/vomiting and asthenia observed in 27 (60%) and 16 (36%) of patients, respectively. One complete and eight partial responses were observed. Conclusion: The combination of PLD and oxaliplatin has an acceptable toxicity profile with promising activity and merits further evaluation in phase II studies.