Background The physicians' acceptance rate of pharmacists' interventions to improve pharmacotherapy can vary depending on the setting. The acceptance rate of interventions proposed by pharmacists located in the hospital pharmacy over the telephone and factors associated with acceptance are largely unknown. Objective To determine the physicians' acceptance rate of pharmacists' interventions proposed over the telephone in daily hospital practice and to identify factors associated with acceptance. Setting A retrospective case-control study was performed concerning adult patients admitted to a university hospital in the Netherlands. Method Pharmacists' interventions, based on alerts for drug-drug interactions and drug dosing in patients with renal impairment, recorded between January 2012 and June 2013 that were communicated over the telephone were included. Factors associated with physicians' acceptance were identified with the use of a mixed-effects logistic model. Main outcome measure The primary outcome was the proportion of accepted interventions. Results A total of 841 interventions were included. Physicians accepted 599 interventions, resulting in an acceptance rate of 71.2%. The mixed-effects logistic model showed that acceptance was significantly associated with the number of prescribed drugs (16 to ≤ 20 drugs OR adj 1.88; 95% CI 1.05-3.35, > 20 drugs OR adj 2.90; 95% CI 1.41-5.96, compared to ≤ 10 drugs) and the severity of the drug-related problem (problem without potential harm OR adj 6.36; 95% CI 1.89-21.38; problem with potential harm OR 6.78; 95% CI 2.09-21.99, compared to clinically irrelevant problems), and inversely associated with continuation of pre-admission treatment (OR adj 0.55; 95% CI 0.35-0.87). Conclusion Over the study period, the majority of pharmacists' interventions proposed over the telephone were accepted by physicians. The probability for acceptance increased for patients with an increasing number of medication orders, for clinically relevant problems and for problems related to treatment initiated during admission.