Importance: A combination of conservative treatments is commonly used in clinical practice for thumb base osteoarthritis despite limited evidence for this approach. Objective: To determine the efficacy of a 6-week combination of conservative treatments compared with an education comparator. Design, Setting, and Participants: Randomized, parallel trial with 1:1 allocation ratio among people aged 40 years and older with symptomatic and radiographic thumb base osteoarthritis in a community setting in Australia. Interventions: The intervention group (n = 102) received education on self-management and ergonomic principles, a base-of-thumb splint, hand exercises, and diclofenac sodium, 1%, gel. The comparator group (n = 102) received education on self-management and ergonomic principles alone. Intervention use was at participants' discretion from 6 to 12 weeks. Main Outcomes and Measures: Hand function (Functional Index for Hand Osteoarthritis; 0-30) and pain (visual analog scale; 0-100 mm) were measured at week 6 (primary time point) and week 12. An α of.027 was used at week 6 to account for co-primary outcomes. Results: Of the 204 participants randomized, 195 (96%) and 194 (95%) completed follow-ups at 6 and 12 weeks, respectively; the mean (SD) age of the population was 65.6 (8.1) years, and 155 (76.0%) were female. At week 6, hand function improved significantly more in the intervention group than the comparator (between-group difference,-1.7 units; 97.3% CI,-2.9 to-0.5; P =.002). This trend was sustained at 12 weeks (-2.4 units; 95% CI,-3.5 to-1.3; P <.001). Pain scores improved similarly at week 6 (between-group difference,-4.2 mm; 97.3% CI,-11.3 to 3.0; P =.19). At week 12, pain reduction was significantly greater in the intervention group (-8.6 mm; 95% CI,-15.2 to-2.0; P =.01). There were 34 nonserious adverse events, all in the intervention group-mostly skin reactions and exercise-related pain exacerbations. Conclusions and Relevance: In this randomized clinical trial of people with thumb base osteoarthritis, combined treatments provided small to medium and potentially clinically beneficial effects on hand function but not pain. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000353493.