Immunostimulatory and antiproliferative therapies have been widely used for the treatment of multiple warts. Recently, anti-HPV activity of ionic contra viral therapy (ICVT) which is comprised of combined digoxin and furosemide has been demonstrated. To evaluate and compare the effectiveness and safety of intralesional injection of Candida antigen, vitamin D3, and combined digoxin and furosemide in the treatment of multiple warts. Seventy-five patients with numerous warts were randomly assigned to one of three equal groups: Candida antigen, vitamin D3, or a combination of digoxin and furosemide. In the Candida antigen group, injections into the biggest wart were done. In the vitamin D3 and combined digoxin/furosemide groups, the agent was injected into each wart with a maximum of five injected warts. Injections were repeated every 2 weeks until clearance or for a total of five sessions. There was a statistically significant difference in the overall therapeutic response among the studied groups in favor of the intralesional Candida antigen group (60%), followed by the vitamin D3 group (48%) and the ionic contraviral therapy group (28%) (p=0.02). However, the difference between both Candida antigen and vitamin D groups was not significant (p=0.59). Intralesional Candida antigen immunotherapy and vitamin D3 antiproliferative therapy are significantly more effective than ICVT. Short follow-up period and relatively small sample size.