In recent issues, the efficacy of chloroquine (and the dosage that may be used) in the treatment of acute chikungunya infections was discussed. We have conducted a double-blind placebo-controlled randomized trial on the French Reunion Island (Indian Ocean), in which 27 patients received chloroquine and 27 patients received a placebo treatment. The chloroquine treatment consisted of 600 mg at day 1, 600 mg at days 2 and 3, and 300 mg at days 4 and 5. No significant difference between groups could be identified regarding the duration of febrile arthralgia or the decrease of viremia between day 1 and day 3. However, at day 200, patients who received chloroquine complained more frequently of arthralgia than those who received placebo (p < 0.01). In conclusion, our results suggest that there is currently no justification for the use of chloroquine to treat acute chikungunya infections.