Abstract Purpose NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. Methods Phase III trial of chemotherapy-free treatment of NovoTTF (20–24 h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. Results Patients (median age 54 years (range 23–80), Karnofsky performance status 80% (range 50–100) were randomised to TTF alone ( n = 120) or active chemotherapy control ( n = 117). Number of prior treatments was two (range 1–6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86 95% CI 0.66–1.12; p = 0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% ( p = 0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p = 0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% ( p = 0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. Conclusions This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.