Background Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with haemolytic anaemia in chronic hepatitis C patients treated with pegylated interferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce. Methods Median haemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic. Results Median Hb drop in 55 patients was greater in rs1127354-CC than -CA/AA (1.8 versus 0.7 g/dl; P=0.029), and in rs6051702-AA than -AC/CC carriers (2.2 versus 1.1 g/dl; P=0.016). Eleven (20%) patients experienced severe anaemia, defined as Hb drop >3 g/dl or to <10 g/dl. All of them were rs6051702-AA. Conclusions Baseline testing of rs6051702 may identify the subset of patients at greatest risk for RBV-induced anaemia using interferon-free hepatitis C therapies.