Seventy-two patients with hand osteoarthritis were randomized to receive either topical cetylated fatty acid (CFA) cream (n = 36) or placebo cream (n = 36), applied twice daily for six weeks. The primary outcome was the Functional Index for Hand Osteoarthritis (FIHOA) at weeks 2, 4, and 6. Secondary outcomes included pain (measured by VAS), Patient Global Assessment (PGA), and skin irritation at the same time points. Overall, the results of the study revealed that patients in the CFA group had significantly lower VAS scores at week 4 and week 6, as well as better PGA scores at week 6, compared to placebo. No significant differences were seen in FIHOA scores. These findings suggest that topical CFA may reduce pain and improve patient-reported outcomes, though not functional outcomes, in hand osteoarthritis.