PurposeOperative treatment of a humeral shaft fracture results in faster recovery than nonoperative treatment. The cost-effectiveness, in terms of costs per Quality-Adjusted Life Year (QALY) gained (Dutch threshold €20,000-€80,000) or minimal important change (MIC) in disability reduced (DASH 6.7), is unknown. The aim of this study was to determine cost-utility and cost-effectiveness of operative versus nonoperative treatment in adults with a humeral shaft fracture type 12A or 12B.MethodsThis study was performed alongside a multicenter prospective cohort study. Costs for health care and lost productivity until one year after trauma were calculated. The incremental cost-utility ratio (ICUR) was reported in costs per QALY (based on the EuroQoL-5D-3L (EQ-5D)) gained. The incremental cost-effectiveness ratio (ICER) was reported in costs per MIC (based on the DASH score at three months) reduced.ResultsOverall, 245 patients were treated operatively and 145 nonoperatively. In the operative group, the mean total costs per patient (€11,925 versus €8793;p< 0.001) and QALYs (0.806 versus 0.778;p< 0.001) were higher. The ICUR of operative treatment was €111,860 per QALY gained (i.e., €3132/0.028). The DASH was 7.3 points (p< 0.001) lower in the operative group. The ICER of operative treatment was €2880 per MIC in disability reduced (i.e., €3132/7.3*6.7).ConclusionDue to the limited effect of treatment on quality of life measured with the EQ-5D, the ICUR of operative treatment (€111,860 per QALY gained) exceeds the threshold. However, the incremental costs of €2880 per clinically meaningful difference in DASH are much lower and suggest that operative treatment for a humeral shaft fracture is cost-effective.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00068-022-02160-1.