A second cholera epidemic struck Malta from 9 June to 13 October 1850. Suspicious cases had occurred in the Manderaggio in May, but the first authentic case occurred in a master of a Maltese boat, four days after his arrival from Susa, Tunisia on 9 June. Two men who had been disembarking cattle from Tunis and a soldier of the Malta Regiment residing with them also died.
Cholera spread to the 44th Regiment at Floriana Barracks. From 25 to 29 June, the 44th Foot had 8 cases with 6 deaths. The soldier's latrines were nothing more than cess pits, with neither flushing nor trapping, whilst the urine tabs and urinals were placed next or inside the doors of the barrack rooms. Encampment and the removal of men from their barracks was widely practiced to combat cholera. The troops were removed to Fort Ricasoli and Isola Gate Barracks. A Company of the 44th Regiment stationed for several months at San Francesco de Paola Barracks lost a third of its men. The Company was removed to Gozo. Within ten days of its arrival, it had no less than 26 men fell ill, with 16 deaths.
Cholera then appeared to the village of Ghajnsielem situated at the foot of Fort Chambray, from where it rapidly spread through out Gozo. There were 105 attacks and 78 deaths among the civilians in Gozo.
Out of a garrison of 3,475 men, 228 became infected with the Vibrio cholera, with 135 deaths. In addition, 407 cases of other bowel complaints were admitted to the military hospital with one death. The garrison had its last case on 23 Sept, but the epidemic did not cease until 20 October. There were 2833 civilians with 1,551 deaths in Malta, with the villages of Qormi and Birkirkara the worst affected.