In concluding his book, Roughing It, Mark Twain remarked on his journey back to New York City:
“When I returned to San Francisco I projected a pleasure journey to Japan and thence westward around the world; but a desire to see home again changed my mind, and I took a berth in the steamship, bade good-bye to the friendliest land and livest, heartiest community on our continent, and came by the way of the Isthmus to New York—a trip that was not much of a picnic excursion, for the cholera broke out among us on the passage and we buried two or three bodies at sea every day.”
He departed San Francisco aboard the steamship America commanded by Edgar "Ned" Wakeman, December 15, 1866 The America belonged to the North American Steamship Company, which offered passage to the East via Nicaragua. The Pacific Mail Steamship Company offered the older Panama route.
The first night out from San Francisco a violent storm nearly swamped the America, terrifying the passengers in steerage and making virtually everyone seasick. “Happily I escaped,” Clemens observed, “had something worse.” This unnamed illness kept him confined, though not completely solitary, both before and during the voyage.
The ship arrived at San Juan del Sur,, on the west coast of Nicaragua, December 28, 1866. Then a 3 day trek across the Isthmus: stage to Virgin Bay, Lake Nicaragua; steamer across the lake and down the San Juan River, to San Juan del Norte (Greytown).
Before the Panama Canal was built the San Juan River was frequently used as a major part of the route from the Atlantic to the Pacific Ocean. Many people, including African slaves and people hoping to find gold in California, were transported via this route. . Tens of thousands took a steamboat that was operated by the Accessory Transit Company, directed by Cornelius Vanderbilt. The boat traveled up the San Juan River and across Lake Nicaragua; a stagecoach completed the connection to the Pacific coast.
At Greytown Twain boarded the steamer San Francisco, January 1, 1867. The ship suffered mechanical problems and on 2 January, one day out of Greytown, cholera struck. By 5 January three were dead and a fourth mortally ill.
The San Francisco was in port at Key West for a day and a night, departing January 7, 1867 and arriving in New York, January 12, 1867 By then seven had died (four from cholera), and there had probably been more deaths among the twenty-one passengers who fled the ship at Key West.
Mark Twain described his arrival in New York for the Alta:
We swore the ship through at quarantine, which was right—she hadn’t had any real cholera on board since we left Greytown—and at 8 o’clock this morning we stood in the biting air of the upper deck and sailed by the snow-covered, wintry looking residences on Staten Island—recognized Castle Garden [in the Battery]—beheld the vast city spread out beyond, encircled with its palisade of masts, and adorned with its hundred steeples—saw the steam-tug and ferryboats swarming through the floating ice, instinct with a frenzied energy, as we passed the [East] river—and in a little while we were ashore and safe housed at the Metropolitan.