To assess the effectiveness of 5% imiquimod cream (IQ) in the treatment of vulvar, penile and anal intraepithelial neoplasias (VIN, PIN and AIN), we searched Medline, Embase, PubMed and Cochrane Library databases. With regard to VIN there were two randomized controlled trials (RCTs), eight uncontrolled/cohort studies, nine case reports and one review article. Use of IQ in PIN and AIN were only supported by cohort studies (two each for PIN and AIN) and case reports (15 for PIN and 3 for AIN). On pooled analysis of RCTs, uncontrolled and cohort studies, the mean complete response (CR) rate for VIN, PIN and AIN were 51%, 70% and 48%, respectively. The mean partial response (PR) rate for VIN, PIN and AIN were 25%, 30% and 34% respectively. The recurrence (RR) rate for VIN, PIN and AIN were 16%, 0% and 36%, respectively. The follow-up period for VIN, PIN and AIN ranged from 2 to 32 months, 10 to 12 months and 11 to 39 months, respectively. Although the results for PIN look the best, the strongest evidence regarding efficacy of IQ in anogenital intraepithelial neoplasia is for VIN supported by RCTs. Evidence for use of IQ in AIN was essentially limited to HIV-positive men who have sex with men. IQ was reasonably well tolerated with side-effects being managed with reduction in frequency of drug usage and/or rest periods. Based on these results, IQ seems to be a safe mode of treatment and is possibly an alternative to currently available methods of treatment. However, there are no comparative studies assessing its efficacy against traditional modes of treatment.