Background.Pyogenic arthritis of the small joints of the hand and wrist is a known but poorly described entity. The objective of this work was to characterize the clinical presentation, antimicrobial treatment, and surgical interventions of native small joint arthritis (SJA) treated in our tertiary center.Methods.According to predefined variables, medical records of adult patients with SJA treated in a Swiss university hospital between 2005 and 2013 were retrospectively analyzed.Results.The median age of 97 patients (101 joints) was 52 years (interquartile range [IQR], 38–68 years); 52% had no comorbidity. Small joint arthritis of the second and third fingers accounted for 53% of infections, with metacarpal-phalangeal and proximal interphalangeal joints most commonly involved. Of 86 (89%) episodes with an exogenous source, 63 (65%) followed a trauma. The most commonly isolated microorganism was Staphylococcus aureus (38%), followed by β-hemolytic streptococci (13%) and Pasteurella spp (11%). Eighty-seven episodes (89 joints) in patients with follow-up examinations were included in treatment and outcome analyses. Up to 2 surgical interventions were required to cure infection in 74 (83%) joints. Median antimicrobial treatment duration was 14 days (IQR, 12–28 days), with amoxicillin/clavulanate administered in 74 (85%) episodes. At follow up, cure of infection was noted in all episodes and good functional outcome in 79% of episodes.Conclusions.Small joint arthritis shows considerable differences from clinical patterns reported for larger joints. In our series, the outcome was good with no more than 2 surgical interventions and median treatment duration of 14 days in 79% of episodes.