To evaluate ThinPrep (Cytyc, Marlborough, MA) processing of endoscopic brushing specimens for cytologic examination, ThinPrep slides and direct smears of 29 gastrointestinal (GI) and 22 bronchial brushings were compared. Clinicians prepared the direct smears. The brush was then immersed in CytoLyt (Cytyc) and one ThinPrep slide made. All cases had corresponding biopsies. Smears and ThinPrep slides were screened and reviewed independently. Screening time per case was recorded. All slides were evaluated for cellularity, quality, cellular preservation, and quantity of diagnostic cells. A diagnosis was rendered for each case. Cytologic and histologic diagnoses were correlated. Follow up was obtained for cases with discrepant histologic and cytologic diagnosis. Twenty-three brushings were from esophagus, 5 stomach, 1 duodenum, and 22 lung. An average of 3.6 direct smears (range 2–6) was made for each case. Average screening time per case was 12 minutes for GI direct smear, 15 minutes bronchial direct smear, 4 minutes GI ThinPrep slide, and 9 minutes bronchial ThinPrep slide. ThinPrep slides were superior to direct smears in cellularity, quantity of diagnostic cells, and quality of slides. ThinPrep slides and direct smears showed comparable cellular preservation. The sensitivity of detecting malignancy by biopsy, direct smears, and ThinPrep slides was 81%, 75%, and 75%, respectively. One false-positive diagnosis was made on cytology with both direct smear and ThinPrep slide, a case with radiation atypia. In conclusion, ThinPrep slides are at least comparable to direct smears in cytologic examination of brushings. However, false-positive diagnosis is a possible potential pitfall.