Abstract Objectives To explore patient characteristics associated with response to intramuscular methylprednisolone (MP) therapy in hand osteoarthritis (OA). Methods We performed an exploratory monocentric retrospective study. Patients with a clinical diagnosis of hand OA who visited our outpatient clinic between July 2016 and June 2021, and received at least once an intramuscular MP injection, were included. Clinical data, including laboratory and radiologic results, were retrieved from electronic patient records (EPRs). Patients’ reported response to MP and its duration in the first six months after injection was based on free text from the EPRs. Response was categorized into three groups: no response or worsening of symptoms, modest response, and good response. Duration of response was categorized as short-term (<2 weeks), or long-term (≥2 weeks). Multivariable logistic regression models were performed to determine factors associated with good response to therapy with methylprednisolone. Results Data from 262 hand OA patients (76% female) were analyzed. A good response was experienced by 150 patients (57.2%). Among those with modest to good response, the perceived response of 162 patients (80.6%) lasted 2 weeks or longer. Univariate regression analysis indicated that the level of CRP was associated with good response (odds ratio(OR) 1.08; 95% CI 1.00 to 1.17). However, multivariate regression analysis showed no statistical significant associations. Conclusion In this retrospective study, more than half of hand OA patients displayed good response to intramuscular MP administration. The possible relation between the presence of low-grade inflammation and the response to this therapy warrants further investigation.