Background Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an effective and safe treatment option for the treatment of actinic keratosis (AK). Incoherent lamps are often used, matching the absorption maxima of ALA. Objectives A comparative trial was performed to evaluate the efficacy of recently developed light-emitting diodes (LEDs). Methods Human epidermal keratinocytes were incubated for 24 h with ALA (100, 200, 300, 400 or 500 mu mol L-1) and irradiated consecutively using either an incoherent halogen lamp (lambda(em)=580-750 nm; 24 J cm(-2); 40 mW cm(-2)) or an LED system (lambda(em)=633 +/- 3 nm; 3, 6, 12 or 24 J cm(-2); 40 mW cm(-2)). Topical ALA-PDT was performed on 40 patients with AK (n=584) in a symmetrical distribution suitable for two-sided comparison. After incubation with ALA (20% in cream base) irradiation was performed with the incoherent lamp (100 J cm(-2); 160 mW cm(-2)) on one side and the LED system (40 J cm(-2); 80 mW cm(-2)) on the opposite side followed by re-evaluation up to 6 months. Results No significant differences between the LED system (3, 6, 12 or 24 J cm(-2)) and the incoherent light source (24 J cm(-2)) regarding cytotoxicity was found in vitro. The complete remission rate yielded in the in vivo investigation was also not significantly different at 6 weeks (P=0.95), 3 months (P=0.75) and 6 months (P=0.61) following therapy. Six weeks following therapy complete remission rates of 84.3% (LED system) and 82.8% (incoherent lamp) were achieved. There was also no significant difference between both light sources regarding pain during light treatment (P=0.67), patient satisfaction (P=1.0) or cosmesis (P=1.0) following therapy. Conclusions These results show the efficacy of an LED system for ALA-PDT both in vitro and in vivo. ALA-PDT with the LED system showed a noninferiority regarding the clinical outcome in the treatment of AK compared with the incoherent lamp.