Although curettage is commonly used to treat molluscum contagiosum, prospective studies on its effectiveness are lacking. To evaluate prospectively the efficacy of curettage in the treatment of molluscum contagiosum and to identify the risk factors associated with treatment failure. A systematic 2-month follow-up survey study was carried out on 73 patients treated by curettage for molluscum contagiosum. Treatment of molluscum contagiosum by curettage was associated with a high risk of treatment failure at week 4 (42/64, 66%) and at week 8 (25/55, 45%). Risk factors for treatment failure at week 4 and 8 were the number of lesions at day 0 (P < 0.001), the number of involved anatomical sites (P < 0.001) and concomitant atopic dermatitis (P = 0.038 and P < 0.001, at weeks 4 and 8, respectively). The main risk factor for treatment failure is lesion number, underlining the importance of the early detection of the lesions or, alternatively, emphasizing the need for therapeutic options other than curettage in patients with numerous lesions.