Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been demonstrated as a feasible procedure in extended liver resections as a means of successfully increasing the volume of the future liver remnant (FLR). Neoadjuvant chemotherapy (CTx) is toxic to the organ and may impair hepatic regeneration. This study was performed to assess the procedure's effect on hypertrophy of the FLR, including the short-term survival. Study design We analyzed 19 consecutive ALPPS patients, of whom 58% (n = 11) received neoadjuvant CTx because of colorectal liver metastasis (CRM). Patients presented with multifocal CRM (n = 11, 58%); cholangiocarcinoma (n = 7, 37%), of which 5 were in the Klatskin position; and gallbladder carcinoma (n = 1, 5%). Hepatectomy was performed within 6 to 13 days after hepatic partition. Volumetry was performed before both liver partitioning and hepatectomy. A survival analysis was performed. Results Liver partition and portal vein ligation induced sufficient hypertrophy of the FLR, with an increased volume of 74% ± 35%. Patients underwent hepatectomy after a median of 8 days; in all cases R0 resection was achieved. Neoadjuvant CTx was shown to significantly impair hypertrophy. The volume of the FLR in non-CTx patients increased by 98% ± 35%; an increase of 59% ± 22% was observed in patients who underwent CTx (p = 0.027). Chemotherapy did not have an impact on either morbidity or in-hospital mortality, which were 68% and 16%, respectively. One-year overall survival was 53%, with a 1-year survival of 67% in CRM patients and 38% in non-CRM patients (p > 0.05). Conclusions Data presented here demonstrate for the first time that neoadjuvant CTx significantly impairs hypertrophy of the FLR after ALPPS.