Aciclovir, also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include the prevention of cytomegalovirus infections following transplant, and severe complications of Epstein–Barr virus infection. It can be taken by mouth, applied as a cream, or injected.

Common side effects include nausea and diarrhea. Potentially serious side effects include kidney problems and low platelets. Greater care is recommended in those with poor liver or kidney function. It is generally considered safe for use in pregnancy with no harm having been observed. It appears to be safe during breastfeeding. Aciclovir is a nucleoside analogue that mimics guanosine. It works by decreasing the production of the virus's DNA.

Aciclovir was patented in 1974, by Burroughs Wellcome, and approved for medical use in 1981. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication and is marketed under many brand names worldwide. In 2023, it was the 150th most commonly prescribed medication in the United States, with more than 3 million prescriptions.

Aciclovir acts by inhibiting viral DNA replication and is used for the treatment of herpes simplex virus (HSV) and varicella zoster virus infections, including:

It has not been found to be effective against Epstein–Barr virus and its associated infectious mononucleosis. Aciclovir risks causing resistance to antiviral agents, and in 1% to 10% of cases can cause unpleasant side effects.

Aciclovir taken by mouth does not appear to decrease the risk of pain after shingles. In those with herpes of the eye, aciclovir may be more effective and safer than idoxuridine. It is unclear if aciclovir eye drops are more effective than brivudine eye drops.

Intravenous aciclovir is effective in treating severe medical conditions caused by different species of the herpes virus family, including severe localized infections of the herpes virus, severe genital herpes, chickenpox and herpesviral encephalitis. It is also effective in systemic or traumatic herpes infections, eczema herpeticum, and herpesviral meningitis. Reviews of research dating from the 1980s show there is some effect in reducing the number and duration of lesions if aciclovir is applied at an early stage of an outbreak. Research shows effectiveness of topical aciclovir in both the early and late stages of the outbreak as well as improving methodologically and in terms of statistical certainty from previous studies. Aciclovir trials show that this agent has no role in preventing HIV transmission, but it can help slow HIV disease progression in people not taking anti-retroviral therapy (ART). This finding emphasizes the importance of testing simple, inexpensive non-ART strategies, such as aciclovir and cotrimoxazole, in people with HIV.

The CDC and others have declared that during severe recurrent or first episodes of genital herpes, aciclovir may be used. For severe HSV infections (especially disseminated HSV), IV aciclovir may also be used.