Summary Background Daylight photodynamic therapy (DL‐PDT) with methyl‐5‐aminolaevulinate (MAL) is an effective treatment for mild and moderate actinic keratosis (AK). Objectives To assess the clinical efficacy, tolerability and cost‐effectiveness of 5‐aminolaevulinic acid nanoemulsion (BF‐200 ALA) compared with MAL in DL‐PDT for grade I–II AKs. Methods This nonsponsored, prospective randomized double‐blind multicentre trial included 69 patients with 767 grade I–II AKs located symmetrically on the face or scalp. A single DL‐PDT was given in a randomized split‐face design. The primary outcome was clearance of the AKs at 12 months as assessed by a blinded observer. The secondary outcomes were pain, treatment reactions, cosmetic outcome and the cost‐effectiveness of the therapy. Results In the per‐patient (half‐face) analysis, clearance was better for the BF‐200 ALA sides than for those treated with MAL (P = 0·008). In total, BF‐200 ALA cleared 299/375 AKs (79·7%) and MAL 288/392 (73·5%) (P = 0·041). The treatment was practically painless with both photosensitizers, the mean pain visual analogue scale being 1·51 for BF‐200 ALA and 1·35 for MAL (P = 0·061). Twenty‐six patients had a stronger skin reaction on the BF‐200 ALA side, seven on the MAL side and 23 displayed no difference (P = 0·001). The cosmetic outcome was excellent or good in > 90% of cases with both photosensitizers (P = 1·000). The cost‐effectiveness plane showed that the costs of DL‐PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF‐200 ALA. Conclusions Our results indicate that BF‐200 ALA is more effective than MAL in DL‐PDT for grade I–II AKs. BF‐200 ALA provides slightly better value for money than MAL. What's already known about this topic? Daylight photodynamic therapy (DL‐PDT) with methylaminolaevulinate (MAL) is effective and practically painless for mild or moderate actinic keratosis (AK). Its long‐term efficacy or cost‐effectiveness is rarely reported. What does this study add? A single treatment with 5‐aminolaevulinic acid nanoemulsion (BF‐200 ALA) was shown in a 12‐month follow‐up to be more effective than MAL for use in DL‐PDT given in a split‐face design for grade I‐II AKs. BF‐200 ALA provides slightly better value for money than MAL. Linked Comment: Dawe. Br J Dermatol 2019; 181:246–247. Plain language summary available online Respond to this article