Pretargeted radioimmunotherapy (PRIT) with the β-emitting radionuclide (177)Lu is an attractive approach to treat carcinoembryonic antigen (CEA)-expressing tumors. The therapeutic efficacy of PRIT might be improved using α-emitting radionuclides such as (213)Bi. Herein, we report and compare the tumor-targeting properties and therapeutic efficacy of (213)Bi and (177)Lu for PRIT of CEA-expressing xenografts, using the bispecific monoclonal antibody TF2 (anti-CEA × anti-histamine-succinyl-glycine [HSG]) and the di-HSG-DOTA peptide IMP288. Methods: The in vitro binding characteristics of (213)Bi-IMP288 were compared with those of (177)Lu-IMP288. Tumor targeting of (213)Bi-IMP288 and (177)Lu-IMP288 was studied in mice bearing subcutaneous LS174T tumors that were pretargeted with TF2. Finally, the effect of (213)Bi-IMP288 (6, 12, or 17 MBq) and (177)Lu-IMP288 (60 MBq) on tumor growth and survival was assessed. Toxicity was determined by monitoring body weight, analyzing blood samples for hematologic and renal toxicity (hemoglobin, leukocytes, platelets, creatinine), and immunohistochemical analysis of the kidneys. Results: The in vitro binding characteristics of (213)Bi-IMP288 (dissociation constant, 0.45 ± 0.20 nM) to TF2-pretargeted LS174T cells were similar to those of (177)Lu-IMP288 (dissociation constant, 0.53 ± 0.12 nM). In vivo accumulation of (213)Bi-IMP288 in LS174T tumors was observed as early as 15 min after injection (9.2 ± 2.0 percentage injected dose [%ID]/g). (213)Bi-IMP288 cleared rapidly from the circulation; at 30 min after injection, the blood levels were 0.44 ± 0.28 %ID/g. Uptake in normal tissues was low, except for the kidneys, where uptake was 1.8 ± 1.1 %ID/g at 30 min after injection. The biodistribution of (213)Bi-IMP288 was comparable to that of (177)Lu-IMP288. Mice treated with a single dose of (213)Bi-IMP288 or (177)Lu-IMP288 showed significant inhibition of tumor growth. Median survival for the groups treated with phosphate-buffered saline, 6 MBq (213)Bi-IMP288, 12 MBq (213)Bi-IMP288, and 60 MBq (177)Lu-IMP288 was 22, 31, 45, and 42 d, respectively. Mice receiving 17 MBq (213)Bi-IMP288 showed significant weight loss, resulting in a median survival of only 24 d. No changes in hemoglobin, platelets, or leukocytes were observed in the treatment groups. However, immunohistochemical analysis of the kidneys of mice treated with 17 or 12 MBq (213)Bi-IMP288 showed signs of tubular damage, indicating nephrotoxicity. Conclusion: To our knowledge, this study shows for the first time that PRIT with TF2 and (213)Bi-IMP288 is feasible and at least as effective as (177)Lu-IMP288. However, at higher doses, kidney toxicity was observed. Future studies are warranted to determine the optimal dosing schedule to improve therapeutic efficacy while reducing renal toxicity.