To compare drug and adverse event costs and cost per successful clinical response with tocilizumab (TCZ) monotherapy vs adalimumab (ADA) monotherapy in patients with rheumatoid arthritis. Patients in the ADACTA trial were randomized to either TCZ 8mg/kg intravenously every 4 weeks or ADA 40 mg subcutaneously every 2 weeks as monotherapy for 24 weeks. Drug costs of $397.71/80-mg vial for TCZ (plus $136 administration cost per infusion) and $2220.62/40-mg for ADA were based on WAC drug prices (July 2017). Outcomes included patient-level drug costs and cost of hospitalization due to adverse events, and cost per response. Cost per response was calculated by dividing the mean drug plus administration cost by the proportion of patients achieving Disease Activity Score–28 joints (DAS28) <2.6 (remission) or American College of Rheumatology response criteria 20%/50%/70% (ACR20/ACR50/ACR70). The proportions of patients achieving DAS28 <2.6, ACR 20, ACR50 and ACR70 were 39.9%, 65.0%, 47.2% and 32.5% for TCZ, respectively, and 10.5%, 49.4%, 27.8% and 17.9% for ADA, respectively; P <0.0001, P=0.0038, P=0.0002, P=0.0023 for TCZ vs ADA, respectively. Hospitalization costs were calculated using the daily hospital cost of $2433 (2017) and number of hospital days. Among the 163 patients treated with TCZ and 162 with ADA, mean total drug and administration costs per patient over 24 weeks were $16,674.74 and $23,357.63, respectively. Mean drug and administration costs were lower per each clinical response achieved with TCZ compared with ADA (DAS28 <2.6: $41,791 vs $222,454; ACR20: $25,653 vs $47,283; ACR50: $35,328 vs $84,020; ACR70: $51,307 vs $130,490). The total hospital days/costs were 32/$77,856 for TCZ and 43/$104,619 for ADA. In this comprehensive comparative assessment, the cost to achieve all four clinical responses was lower for patients receiving TCZ than for ADA.