Background: Patients with rheumatoid arthritis may be resistant to conventional treatment with disease-modifying antirheumatic drugs (DMARDs). On the other hand, biologic therapy is costly and may be inconvenient for many patients. Pamidronate is a potent bisphosphonate with the capacity of modifying the biological activity of the immune system cells. It may thus be used as an anti-inflammatory agent in patients with inflammatory joint diseases. Materials and Methods: To assess the effectiveness of pamidronate in the management of rheumatoid arthritis, we selected 38 patients with rheumatoid arthritis to enroll in a pilot study to receive pamidronate and conventional treatment with prednisolone and DMARDs in combination. These patients received 60 mg of pamidronate for 3 consecutive months and were followed for 6 months since the first infusion. Results: The mean visual analogue score (VAS) and disease activity score (DAS28) fell steadily until one month after the third infusion. However, no improvements were observed during the 3 months after the last infusion of the drug. All patients, except one, reported decreased pain in response to 3 consecutive pulses of pamidronate and most had improvements in the assessed laboratory and clinical indices. The drug was tolerated well in our patients. Conclusion: Pamidronate infusions had beneficial effects on various clinical and laboratory parameters of patients, but alleviation of symptoms were temporary and did not last for more than 6 months. This treatment option can be a choice for difficult cases of rheumatoid arthritis with severe pain and osteoporosis.