Information about the distribution of effusion within the arthritic knee joint should be considered in selecting an anatomical approach for arthrocentesis. We recorded ultrasound measurements of fluid distribution in the knees of patients attending our clinic for knee injections under ultrasound guidance. In a cross-sectional observational study, we used high-resolution ultrasound (US) to record measurements of maximum fluid depth in the medial, midline and lateral regions of the suprapatellar pouch (SPP) in 46 patients with arthritis attending for routine US-guided injection of the knee. Mean fluid depth [in millimetres, (SD)] was significantly greater in the lateral SPP [9.2 (5.1)] than in the medial [6.5 (4.6)] or the midline [5.9 (3.7)] regions with the knee in relaxed full extension (p < 0.001 for comparison of lateral SPP with both midline and medial SPP). Small effusions were more commonly detected in the lateral SPP than elsewhere. In patients with painful knee arthritis, fluid distributes maximally to the lateral SPP in the extended knee. This has implications regarding the anatomical approach to arthrocentesis that clinicians should choose to perform and teach.