OBJECTIVES: To systematically review the currently available clinical and cost-effectiveness evidence of non-pegylated liposomal doxorubicin (NPLD) for non-Hodgkin lymphoma (nHL). The hypothesis under verification was that the administration of NPLD lowers the cardiotoxicity typical for conventional anthracyclines while being able to sustain the clinical effect of treatment. METHODS: A systematic literature search was conducted for clinical  and cost-effectiveness data for the nHL population treated with NPLD, using the main medical databases (PubMed, EMBASE, Cochrane Library). In addition, clinical trial registries were searched, reference lists of included studies and  reviews were screened for missed studies. Searches took place in September 2012. RESULTS: The review generated 9 one-arm clinical trials and 1 retrospective study which met the inclusion criteria. One comparative parallel trial comparing R-CHOP with R-COMP in the DLBCL population is ongoing, with no results published. Generally, available evidence is poor – studies identified are characterized by many limitations, i.e.: small and heterogeneous study populations, relatively short observation period, not always specified inclusion and exclusion criteria, diversified treatment regimens (with R-CHOP dominating), shortened or/and presented selectively safety data. The majority of studies was performed in the DLBCL population. Cumulative interpretation of data was hindered due to essential differences in between trials.  Lowering of LVEF was observed with a frequency of 0% to 31,7% of cases, while symptomatic lowering of LVEF with the development of chronic ischemic heart disease occurred with the frequency of 0 to 10%. The second most frequent cardiological event observed was arrhythmia. Clinical efficacy focused on surrogate endpoints (radiological responses), defined differently in between trials. No economic evaluations studies were found. CONCLUSIONS: There is limited evidence on the effectiveness and safety of NPLD in patients with nHL due to the lack of well‑designed and well-reported comparative studies. Further research is needed to explore the hypothesis in question.