Buying stocks is easy. It's the holding part that can be difficult. For some investors, inherent volatility scares them into selling stocks too early. In other cases, the underlying business turns out to be less resilient than desired.

However, the best stocks have excellent long-term growth prospects and are worthy of keeping in your portfolio. Here are three unstoppable stocks to buy and hold for the next 20 years.

1. Brookfield Infrastructure

President Joe Biden has called the next 10 years America's "infrastructure decade." It could be even more appropriate to include the rest of the world and add at least another decade or two to the time frame.

There will be plenty of winners with the major global emphasis on infrastructure in the coming years. I think that Brookfield Infrastructure (BIP 0.23%) (BIPC 0.47%) will be among them. The company owns cell towers, data centers, electricity distribution lines, pipelines, rail operations, semiconductor manufacturing foundries, toll roads, and more. 

Brookfield Infrastructure believes that it can deliver organic funds-from-operations (FFO) growth of 6% to 9% per year. Business development deals can boost that growth even more. The company recently announced that it's acquiring a co-controlling stake in North American data center operator Compass Datacenters. It closed on the acquisition of European data center business Data4 last month. Brookfield Infrastructure also expects to finalize its acquisition of intermodal freight container company Triton by Sept. 28.

While growth investors should like Brookfield Infrastructure, income investors will probably love this stock. The distribution yield for its limited partnership (which trades under the BIP ticker) currently stands at nearly 4.8%. The yield for its corporate entity (which trades under the BIPC ticker) is over 4%. 

2. Microsoft

Which technologies are the most important ones to watch over the next 20 years? I suspect that artificial intelligence (AI), augmented reality/virtual reality (AR/VR), cloud computing, and quantum computing would be near the top of the list for most people.

It might seem unrealistic to expect a company to be a leader in all of those areas. But Microsoft (MSFT -0.68%) isn't an ordinary company. The tech giant pioneered software for personal computers. And now it's well positioned to keep its track record of success going in the technologies of the future.

Microsoft already ranks as the second-largest cloud services provider with its Azure platform. It's also at the forefront of incorporating generative AI into its products as a result of the company's partnership with ChatGPT developer OpenAI. Microsoft has also invested heavily in AR/VR and quantum computing.

I predict that AI will be the main growth driver for Microsoft over the next two decades. The company's core focus is on helping organizations improve productivity. AI is a perfect fit for that goal.

3. Vertex Pharmaceuticals

Imagine a drugmaker that enjoyed a monopoly in a multibillion-dollar market and was on track to launch three new products by mid-2025 with the potential for sales of well over $1 billion. Now imagine that this company also was in pole position to develop a cure for type 1 diabetes (T1D).

You actually don't have to use your imagination. Vertex Pharmaceuticals (VRTX 2.84%) is that company. And there's even more to the story.

Vertex certainly commands a monopoly in treating the underlying genetic cause of cystic fibrosis (CF). It expects to announce results by early 2024 from a late-stage study of a new triple-drug combo that's likely to be its most powerful and most profitable CF therapy yet. 

That combo is one of the three new blockbusters potentially on the way for Vertex. The big biotech also awaits regulatory approvals for exa-cel in treating (actually, curing) rare blood disorders sickle cell disease and transfusion-dependent beta thalassemia. Vertex has late-stage results on the way by early next year for non-opioid pain drug VX-548 as well.

In addition, Vertex is leading the way to develop a cure for type 1 diabetes. The company already has three T1D programs in phase 1/2 clinical testing.

If that's not enough, Vertex's pipeline also features yet another drug in pivotal testing. Inaxaplin targets APOL1-mediated kidney disease. This disease affects more patients globally than CF does.

Is Vertex an unstoppable stock to buy and hold for the next 20 years? I think the answer is clearly yes.