It’s been nearly four years since Johnny Depp last donned his signature dreadlocks and adopted his brogue in Disney’s hit franchise “Pirates of the Caribbean.”

This weekend, the Mouse is poised to pillage the worldwide box office yet again with the fourth installment, “On Stranger Tides,” opening in more than 70 overseas markets. In the U.S., pic debuts in 4,155 locations, of which about 2,700 will be 3D-equipped.

“Stranger Tides” kickstarted its overseas launch on Wednesday with a series-best $18.5 million from 10 territories, putting the film on track to surpass the earlier “Pirates” entries.

Domestically, however, the franchise’s fourth pic isn’t expected to set a series benchmark as pre-weekend tracking suggests the film will open in the $90 million-$100 million range.

But B.O. observers shouldn’t wager too many doubloons on that prediction, considering box office has been highly unpredictable lately.

“You also have to add the Depp factor,” advised Disney distrib topper Chuck Viane.

As it stands, the second “Pirates” installment, 2007’s “Dead Man’s Chest,” touts the franchise’s best domestic opening at $135.6 million, followed by third pic “At World’s End,” with $114.7 million the year before.

“Stranger Tides” is the only new wide entry to tempt moviegoers, though holdovers Universal’s “Bridesmaids” and Paramount’s “Thor” should continue attracting filmgoers. “Bridesmaids” could very likely surpass “Thor” in the weekend standings based on No. 1 rankings for the bawdy comedy through Wednesday. “Bridesmaids” has cumed $35.6 million domestically; “Thor,” $127.7 million.

Only a handful of specialty titles are bowing or expanding this weekend, most notably Woody Allen’s “Midnight in Paris,” which Sony Pictures Classics is launching at six locations in New York and L.A.

“Stranger Tides” marks several “Pirates” franchise firsts: It’s the only pic in the series to launch in 3D, as well as Imax, and the first to be greenlit under new Disney head Rich Ross.

Budgeted at a reported $150 million, considerably less than its previous installments, “Stranger Tides” is tracking strongly with the Imax format and will see some uptick from premium 3D ticket prices. Pic is debuting at 257 domestic Imax runs — the most ever for Imax — with an additional 139 screens internationally.

Of the film’s key overseas markets to bow on Wednesday, the biggest contributors were France, the U.K. and Russia, the last of which contributed $5 million — an all-time industry best opening in that territory. It’s the apparent payoff for Disney hosting one of its global premieres for “Stranger Tides” in Moscow last week.

In Blighty, “Stranger Tides” sailed away with $3.2 million, slightly more than “At World’s End,” while French auds shelled out $3.3 million, 17% more than they did for the series’ third entry.

Stateside turnout will be more difficult to gauge with next week’s R-rated “The Hangover Part II” still hogging considerable pre-audience awareness. Still, according to market research services, “Stranger Tides” has extremely high interest among Latino audiences, more than with Caucasian auds, in fact. Strong ethnic turnout could help the film reach at least $100 million for the weekend — the mark Disney has set for itself.

But when all is said and done this weekend, “Stranger Tides” should be a significant worldwide player, easily the year’s best global opener — at least until the rest of this summer’s tentpole offerings have a chance to flex their muscles.