OBJECTIVES: Doxorubicin is an anthracycline used in the treatment of breast cancer, but its use is limited by cumulative dose-dependent cardio-toxicity. Pegylated liposomal doxorubicin is novel drug delivery system that alters bio-distribution of doxorubicin resulting in reduced cardio-toxicity. Our aim is to compare the efficacy and cardio-toxicity of pegylated liposomal doxorubicin and conventional doxorubicin in first-line treatment of metastatic breast cancer (MBC). METHODS: The literature databases (Cochrane Library, EMBASE and PUBMED) were searched from inception to May 2010. Randomised controlled trials assessing the efficacy and cardio-toxicity of pegylated liposomal doxorubicin compared to conventional doxorubicin in first-line treatment of MBC were included. Two reviewers independently selected trials, assessed quality, extracted data and a third reviewer resolved discrepancies. The fixed effects meta-analysis was performed in STATA 9.0 using a standard meta-analysis approach.    RESULTS: Two studies assessing pegylated liposomal doxorubicin with conventional doxorubicin for first-line treatment of MBC met the study criteria. Overall survival (HR = 0.869 [95% CI; 0.720, 1.049]) and overall response rate (RR = 0.908 [95% CI; 0.725, 1.139]) were comparable between the 2 arms. Treatment with pegylated liposomal doxorubicin resulted in significant reduction in cardio-toxicity as compared to conventional doxorubicin (RR = 0.312 [95% CI; 0.198, 0.490]). The results of random effect analysis were similar (data not shown). CONCLUSIONS: Pegylated liposomal doxorubicin provides comparable antitumor activity in terms of efficacy and is better tolerated as compared to conventional doxorubicin in the treatment of MBC. Thus, the liposomal drug delivery system can play a significant role in the use of doxorubicin in MBC treatment which is otherwise limited by its cardio-toxicity and supports its use in first-line treatment of MBC.