An intraindividual left-right comparison of topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) versus topical 5% imiquimod cream was conducted in 30 patients with actinic keratoses (AKs). Patients received 2 ALA-PDT sessions and 1-2 courses of imiquimod three times per week for 4 weeks each. The efficacy endpoint included the individual AK clearance rate. Cosmetic outcomes and patient preferences were also noted. Assessments were completed at 1 and 6 months post-treatment. The 1-month complete AK clearance rate was 70.16% in the ALA-PDT group and 18.26% in the imiquimod group (P < 0.05). The corresponding rates at 6 months were 65.32% and 55.65%, respectively (P > 0.05). There was no significant difference in cosmetic outcome ...