We conducted a prospective, multicenter, phase 3, open-label study to assess long-term sustained clearance of superficial basal cell carcinomas (sBCCs) treated with imiquimod cream 5%. A biopsy-confirmed tumor (area > or = 0.5 cm2 and diameter < or = 2.0 cm) was treated once daily 7 times per week for 6 weeks. Participants with initial clinical clearance at 12 weeks posttreatment were followed for 60 months. Tumor recurrence, serious adverse events (AEs), local skin reactions (LSRs), and skin quality assessments (SQAs) were measured. The initial clearance rate was 94.1% (159/169). Estimated sustained clearance (proportion of participants who achieved initial clearance at the 12-week posttreatment visit and remained clinically clear at each time point during the long-term follow-up period; N=157) was 85.4% at 60 months (life-table method: 95% confidence interval [CI], 79.3%-91.6%). The overall estimate of treatment success was 80.4% at 60 months (N=169; 95% CI, 74.4%-86.4%). Of 20 recurrent tumors, 74 (70%) occurred within the first 24 months of follow-up. Local skin reactions and application site reactions, the AEs reported by the most participants, occurred predominantly during the treatment period and resolved posttreatment. Compared to baseline, investigator-assessed SQA scores for the target tumor site improved for skin surface abnormalities and hyperpigmentation, and worsened for hypopigmentation. For low-risk sBCCs, daily application of imiquimod for 6 weeks had high initial and 5-year sustained clearance rates.