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Objective A randomised controlled study performed from 2007 to 2008 showed beneficial effects of a composite clinical pharmacist service as regards a simple health status instrument. The present study aimed to evaluate if the intervention was cost-effective when evaluated in a decision-theoretic model. Design A piggyback cost-effectiveness analysis from the healthcare perspective. Setting Two internal medicine wards at Sahlgrenska University Hospital, Göteborg, Sweden. Participants Of 345 patients (61% women; median age: 82 years; 181 control and 164 intervention patients), 240 patients (62% women, 82 years; 124 control and 116 intervention patients) had EuroQol-5 dimensions (EQ-5D) utility scores at baseline and at 6-month follow-up. Outcome measures Costs during a 6-month follow-up period in all patients and incremental cost-effectiveness ratio per quality-adjusted life-year (QALY) in patients with EQ-5D utility scores. Inpatient and outpatient care was extracted from the VEGA database. Drug costs were extracted from the Swedish Prescribed Drug Register. A probabilistic analysis was performed to characterise uncertainty in the cost-effectiveness model. Results No significant difference in costs between the randomisation groups was found; the mean total costs per individual±SD, intervention costs included, were €10 748±13 799 (intervention patients) and €10 344±14 728 (control patients) (p=0.79). For patients in the cost-effectiveness analysis, the corresponding costs were €10 912±13 999 and €9290±12 885. Intervention patients gained an additional 0.0051 QALYs (unadjusted) and 0.0035 QALYs (adjusted for baseline EQ-5D utility score). These figures result in an incremental cost-effectiveness ratio of €316 243 per unadjusted QALY and €463 371 per adjusted QALY. The probabilistic uncertainty analysis revealed that, at a willingness-to-pay of €50 000/QALY, the probability that the intervention was cost-effective was approximately 0.2. Conclusions The present study reveals that an intervention designed like this one is probably not cost-effective. The study thus illustrates that the complexity of healthcare requires thorough health economics evaluations rather than simplistic interpretation of data., Article summary Article focus Clinical pharmacist services have been shown beneficial for patient health and healthcare costs, although results are inconsistent. In the present article, we present combined data on costs and health outcomes for a composite clinical pharmacist service. Key messages Although our composite clinical pharmacist service has previously been shown beneficial as regards a simple health status instrument, the incremental cost-effectiveness ratio per QALY was high, more than €460 000 in the base case and more than €100 000 in most sensitivity analyses. Strengths and limitations of this study This study is the first one to provide data on costs per QALY for an in-hospital intervention aimed to improve drug treatment. An important limitation may be that the pharmacists acted like external consultants rather than an integrated part in healthcare, and further research on cost-effectiveness of pharmacist services may be called for.