What are the benefits and risks of treatments for cold sores (herpes labialis)?

Key messages

• Compared with an inactive (dummy) treatment, aciclovir and penciclovir creams probably speed up cold sore healing by about one day without increasing the risk of unwanted events. Compared with each other, both creams may have a similar effect on healing time and a similar risk of unwanted events. Compared with an inactive treatment, aciclovir tablets may result in little to no difference in cold sore healing time, but valaciclovir tablets speed up healing by about one day.

• Unwanted events were uncommon across treatments.

• Agreeing on a standard set of outcomes for cold sore studies would make research easier to compare and help clinicians worldwide choose better treatments.

What are cold sores?

Cold sores (also known as fever blisters or herpes labialis) are painful blisters that develop around the lips and mouth, caused by the herpes simplex virus. They are common and contagious, and many people who get cold sores get them repeatedly. The discomfort and self-consciousness cold sores cause can affect people's well-being. In some cases, untreated cold sores can lead to severe complications.

What treatments are available for cold sores?

Standard treatments for cold sores aim to stop the virus from multiplying. They include antiviral creams that are applied directly to the sore (such as aciclovir and penciclovir) and antiviral tablets taken by mouth (such as aciclovir and valaciclovir). Other treatments are less widely available or are still experimental.

What did we want to find out?

We wanted to know which treatments for cold sores can speed up healing and relieve symptoms. We also wanted to know whether cold sore treatments have any unwanted effects.

What did we do?

We looked for studies that compared cold sore treatments with dummy treatment (placebo), no treatment, or other active treatments in people with healthy immune systems who get cold sores. We combined data from studies to identify patterns and overall results, and we rated our confidence in the evidence based on factors such as study methods and sizes.

We were mainly interested in the most common cold sore treatments, but we collected evidence for all types of treatment.

What did we find?

We included 87 studies involving 22,631 people (mostly women). The studies took place in Europe, North America, Australia, and Asia, and tested 58 treatments in total. Study lengths varied, but most followed people through a single cold sore episode.

Most studies (84 out of 87) reported how long the cold sore took to heal. Just over half (49 studies) reported information about serious unwanted effects that caused people to stop treatment, and 58 studies reported information about mild or moderate adverse events.

The pharmacological industry funded 43 of the studies, non-profit organisations funded 25, one study reported no funding, and 18 studies did not report their funding source.

Main results

As well as healing time and unwanted events, we were also interested in how treatments affect improvement in symptoms, cold sore severity, and pain severity. However, no studies of the most common treatments provided results that we could analyse for these outcomes.

Antiviral creams compared with placebo

Compared with placebo:

• aciclovir cream probably speeds up cold sore healing time by about one day (evidence from 7 studies with 3475 people) without increasing the risk of serious unwanted events (9 studies, 6574 people) or mild or moderate unwanted events (8 studies, 6525 people);

• penciclovir cream probably speeds up cold sore healing time by about one day (1 study, 528 people), without increasing the risk of serious unwanted events or mild or moderate unwanted events (2 studies, 3598 people).

Antiviral tablets compared with placebo

Compared with placebo:

• aciclovir tablets may have little or no effect on healing time (1 study, 145 people);

• valaciclovir tablets speed up healing by about one day (2 studies, 1218 people).

The aciclovir study did not report information on unwanted events. In the valaciclovir studies, no serious unwanted events occurred, and the number of people with mild or moderate unwanted events was similar in people using valaciclovir and people using placebo (2 studies, 1856 people).

Penciclovir cream compared with aciclovir cream

Penciclovir cream and aciclovir cream may have similar effects on healing time and a similar risk of mild or moderate unwanted events (1 study, 225 people). No serious unwanted events occurred in this study.

Aciclovir cream compared with aciclovir tablets

We were interested in comparing the effect of aciclovir cream and aciclovir tablets, but we found no studies comparing them.

What are the limitations of the evidence?

We have moderate or little confidence in most of the evidence for common cold sore treatments, mainly because the studies were small. Newer treatments such as photodynamic therapy, laser treatments, zinc patches, and topical propolis may provide additional benefits but are supported by limited evidence.

Most studies included adults, so we are less confident about how these treatments work in children. In addition, few studies took place in East Asia and in low-resource settings.

How up to date is this evidence?
This review includes studies published up to 23 September 2025.