Intravenous regional blocks (IVRBs) with ketorolac and lidocaine have been reported to be useful in the treatment of complex regional pain syndrome (CRPS). This is the first controlled prospective study of IVRB with lidocaine and ketorolac for treatment of pain and edema in CRPS of the lower extremity in adults. A prospective, randomized, double-blinded, crossover design was used. The primary outcome was overall pain numeric rating scale (NRS) at 1 week postinjection; secondary outcomes included pain with motion, allodynia, joint pain score, edema, range of ankle motion, skin temperature, and short-term pain relief. Ten of 12 adult patients diagnosed with unilateral lower extremity CRPS (type I) completed the study. Four IVRBs were performed 1 week apart in a random sequence with 50 mL lidocaine 0.5% and 0, 30, 60, and 120 mg ketorolac. Only 1 outcome achieved significant improvement; there was 1 day of significant pain reduction in the ketorolac groups (median NRS 6 to 4, P=0.002). Overall pain NRS (10-point scale, mean±SE) at 1 week was 6.2±0.53, 6.5±0.89, 6.0±0.88, 5.9±0.82, and 5.8±0.9 at baseline, 0, 30, 60, and 120 mg, respectively (P=0.8). Pain with movement was 7.15±0.69, 5.7±1.07, 6.1±0.86, 5.0±0.97, and 5.6±0.86, (P=0.059). Edema was not significantly reduced (2% reduction, P=0.6). IVRB with ketorolac and lidocaine produced only short-term pain reduction in patients with CRPS involving the lower extremity after 4 serial injections in our study group. Prospective study is warranted, particularly in the pediatric population.