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Background The aim of this study was to evaluate the impact of all minor and major complications on treatment-related healthcare costs in patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal metastases (PMs). Method Patients with histologically proven colorectal PMs who underwent CRS + HIPEC from March 2006 to October 2019 in a tertiary referral centre were retrospectively identified from a prospectively maintained database. Patients were divided into six subgroups according to the severity of the complications, which were scored using the comprehensive complication index (CCI) (CCI 0–9.9, CCI 10–19.9, CCI 20–29.9, CCI 30–39.9, CCI 40–49.9, and CCI 50 or higher). Treatment-related healthcare costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the chi-squared test and Kruskal–Wallis H test. Results A total of 142 patients were included (CCI 0–9.9, 53 patients; CCI 10–19.9, 0 patients; CCI 20–29.9, 45 patients; CCI 30–39.9, 14 patients; CCI 40–49, 9 patients; and CCI 50 or higher, 21 patients). Median (interquartile range) treatment-related healthcare costs increased significantly and exponentially for the CCI 30–39, CCI 40–49, and CCI 50 or higher groups (€48 993 (€44 262–€84 805); €57 167 (€43 047–€67 591); and €82 219 (€55 487–€145 314) respectively) compared with those for the CCI 0–9.9 and CCI 20–29.9 groups (€33 856 (€24 433–€40 779) and €40 621 (€31 501–€58 761) respectively, P < 0.010). Conclusion Treatment-related healthcare costs increase exponentially as more complications develop among patients who undergo CRS + HIPEC for the treatment of colorectal PMs. Anastomotic leakages after CRS + HIPEC lead to an increase of 295 per cent of treatment-related healthcare costs.