Objective:To evaluate the effect of two-step irradiance schedule on pain control during and clinical efficacy of aminolevulinic acid (ALA) -based photodynamic therapy (PDT) for moderate to severe acne.Methods:Sixty patients with moderate to severe acne were enrolled from the Department of Dermatology, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from January 2018 to March 2019, and equally divided into 2 groups according to the order of treatment: control group receiving conventional irradiation at a light output intensity of 65 mW/cm 2 for 20 minutes, and observation group irradiated at an initial light output intensity of 40 mW/cm 2 for 8 minutes until the irradiation energy reached 20 J/cm 2, followed by irradiation at a light output intensity of 65 mW/cm 2 for 15 minutes until the total irradiation energy reached 78 J/cm 2. During the treatment, the irradiation intensity was appropriately adjusted according to the patients′ response, and all the patients were treated once every 2 weeks for 3 consecutive sessions. The time to onset of pain and pain scores at 5, 10, 15, 20, 25, 30 and50 minutes after the start of irradiation were recorded and compared between the two groups; clinical efficacy was evaluated 1 month after the end of the treatment; other adverse reactions were recorded during the treatment and 3-month follow-up after the end of treatment. Results:The time to onset of pain was significantly different between the observation group (10.40 ± 1.13 minutes) and the control group (3.95 ± 0.77 minutes; t = 25.919, P < 0.05). During the treatment, the pain score significantly changed over time ( F = 323.631, P < 0.01), and significantly differed between the observation group and control group ( F = 89.338, P <0.01). Additionally, there was a significant interaction between the treatment duration and treatment methods ( F = 24.059, P < 0.01). At 5, 10 and 15 minutes after the start of irradiation, the pain score was significantly lower in the observation group than in the control group ( t = 21.714, 28.407, 28.286 respectively, all P < 0.05) ; at 20 minutes, there was no significant difference in the pain score between the two groups ( t = 1.505, P > 0.05) ; at 25 minutes (that is, 2 and 5 minutes after the end of irradiation in the observation group and control group respectively), 30 minutes, 50 minutes (that is, the end of the cold compress), there was also no significant difference in the pain score between the two groups ( t = 0.606, 1.038, 0.344 respectively, all P > 0.05) ; at the end of irradiation (that is, 23 and 20 minutes after the start of irradiation in the observation group and control group respectively), there was still no significant difference in the pain score between the two groups ( t = 1.968, P = 0.149). One month after the 3 sessions of treatment, there was no significant difference in the response rate between the observation group (90%, 27/30) and control group (83.3%, 25/30; χ2 = 0.577, P = 0.706). Moreover, there was no significant difference in the incidence of blisters, erythema, edema, skin dryness, desquamation, pruritus, reactive acne or pigmentation between the two groups (all P > 0.05) . Conclusion:The two-step irradiance schedule can effectively control related pain during the treatment of moderate to severe acne with ALA-PDT, especially in the initial stage of treatment, making patients successfully complete 3 sessions of ALA-PDT treatment and ensuring the clinical efficacy.