Postoperative thrombocytopenia following hepatic cryotherapy has been well documented and shown to be significantly greater than in control patients who had an identical incision or major laparotomy. Serum aspartate transaminase (AST) levels have been used as a reliable indicator of hepatocellular destruction. This study reviews 65 consecutive hepatic cryotherapy operations. We have excluded all patients who had repeat cryotherapy to lesions (n = 6), all who had a colonic or hepatic resection procedure (n = 7), all who had tumors other than colorectal metastases (n = 5), patients with inadequate data (n = 9), and those who were asplenic (n = 2). Of the remaining 36 patients, 14 were treated with a single freeze/thaw cycle, 12 were treated with a double freeze/thaw cycle, and 10 were treated with mixed single and double freezes. The most common platelet nadir was day 3 (n = 21) followed by day 2 (n = 11), with the remaining platelet nadirs being day 1 or 4 (n = 4). The percentage fall in platelet count was found to correlate with the rise in day 1 AST level (r(2) = 0.74, least squares linear regression). The double freeze/thaw cycle patients had a significantly greater fall in platelet count (p = 0.01, Mann-Whitney two sample test). Another institution has reported three deaths due to multiple problems, including coagulopathy in patients treated with double freeze/thaw cycle cryotherapy. The conclusions of this study are that a high AST level on day 1 is a good predictor of impending thrombocytopenia, and that double freeze/thaw cycle cryotherapy results in marked thrombocytopenia, which may be responsible for the coagulopathy seen in some of these patients.