Intra-articular hyaluronic acid (HA) is widely used to treat symptomatic osteoarthritis (OA) in the carpometacarpal joint (CMCJ) of the thumb. However, although apparently effective and relatively safe, intra-articular HA injections act relatively slowly. Therefore, a nonsteroidal anti-inflammatory drug could be added for more prompt pain relief. The aim of this study was to compare the efficacy and safety of ultrasound (US)-guided intra-articular injection of HA and ketorolac with that of HA alone in patients with OA of the CMCJ of the thumb.Seventy-four patients identified by chart review to have a diagnosis of OA of the CMCJ of the thumb received either a US-guided intra-articular injection of 0.5 mL of sodium hyaluronate and 0.5 mL of ketorolac (n = 38) or 0.5 mL of sodium hyaluronate and 0.5 mL of saline (n = 36). Disabilities of the arm, shoulder, and hand (DASH) and verbal numeric scale (VNS) pain scores were recorded before and 1, 3, and 6 months after injection. Univariable analyses (using the chi-squared test) and multiple logistic regression analysis were performed to evaluate the relationship between potential predictors of the outcome (treatment allocation, patient age and sex, duration of pain, and Eaton-Littler classification) and therapeutic effects.The DASH and VNS scores were improved at 1, 3, and 6 months postinjection in both groups. The onset of pain relief was significantly more rapid (at 1 month) after the injection containing HA and ketorolac than after the injection containing HA alone. In 55.3% of cases, pain and function were improved postinjection compared with baseline and remained so for up to 6 months. The success rate was not significantly different between the assessments at 1, 3, and 6 months, and the univariable analyses did not identify any statistically significant potential predictors of the outcome. Multiple logistic regression analysis did not identify any independent predictors of a successful outcome at midterm follow-up.The onset of analgesic action was more rapid after an injection containing HA and ketorolac than after 1 containing HA alone in patients with OA of the CMCJ of the thumb. There were no serious complications.