The clinical significance of minimal acute rejection (grade A₁) in lung transplant recipients is unknown. We prospectively analyzed 1,159 transbronchial lung biopsies in 184 patients. Two hundred seventy-nine biopsies in 128 participants confirmed A₁ histology at a mean postoperative day of 229 ± 340. Sixty four of 255 surveillance A₁ lesions progressed to high-grade acute rejection by 3 months of follow-up, whereas 40 developed new lymphocytic bronchiolitis. Twenty-four A₁ biopsies were symptomatic, with only two cases progressing to high-grade rejection after steroid therapy. Seventy-eight of 184 patients experienced multiple (⩾ 2) A₁ biopsies in the first 12 months after transplant. Bronchiolitis obliterans syndrome developed in 68% of patients with multiple A₁ lesions at a mean of 599 ± 435 days, compared with 43% of patients with one or less A₁ lesions at a mean of 819 ± 526 (p = 0.022). Eighteen patients experienced multiple A₁ biopsies after transplant in the absence of high-grade rejection episodes yet also developed earlier obliterative bronchiolitis (456 ± 245 days, p = 0.020). We conclude that for A₁ transbronchial lung biopsies, the conventional treatment of observation only is now challenged even in patients who are asymptomatic. Patients who experience multiple A₁ lesions develop an earlier onset of obliterative bronchiolitis and may warrant alternative immunosuppressive strategies.