OBJECTIVES: The objective was to assess the improvement in quality of life outcomes with interferon-alpha compared to sunitinib in treatment-naïve advanced/metastatic renal cell carcinoma in patients. METHODS:  Studies were retrieved from Embase, Pubmed, Cochrane and DARE databases using relevant search strategies. Randomised controlled trials which compared IFN with sunitinib were included according to pre-specified inclusion/exclusion criteria. The quality of life (QoL) data presented in the studies was independently extracted by two reviewers and differences were reconciled by a third reviewer. All studies were critically appraised and data was analysed using STATA version 9.2. RESULTS:  Of the 463 studies identified, 3 studies met the inclusion criteria. FKSI-DRS index was reported in one study with baseline and endpoint values as 29.55 and 27.4 with IFN-α and 29.74 and 29.4 with sunitinib (p<0.0001). FKSI-15 index was reported in two studies with mean baseline and endpoint values as 46.1 and 42.1 with IFN-α and 46.45 and 45.3 with sunitinib (p<0.0001). FACT-G score was reported in one study. The baseline FACT-G score was 81.25 with IFN-α and 82.3 with sunitinib. The endpoint FACT-G score was 76.8 with IFN-α and 82.3 with sunitinib (p<0.0001). EQ-5D score was reported in two of the included studies and was reported to be 0.76 and 0.73 as mean baseline and endpoint score for IFN-α group and 0.76 and 0.76 for sunitinib group. EQ-VAS score was reported in one study and was 71.43 and 68.7 as baseline and endpoint for IFN-α group and 73.8 and 73.4 for sunitinib group. The overall survival rate and response rate was better with sunitinib as compared to IFN-α. CONCLUSIONS: Improvement in quality of life outcomes was better in patients treated with IFN-α as compared to sunitinib at the endpoint. IFN-α continues to remain a treatment of choice despite of limited efficacy and tolerability.