The Peregrine Falcon (Falco peregrinus) breeds locally in the Guerrero Negro wetland complex, Baja California Sur, Mexico, but the most recent investigation of their breeding ecology in this wetland area was in 1998. Our objectives were to update the information on the reproduction of Peregrine Falcons in Guerrero Negro and to evaluate the relationship of reproductive parameters with the environmental temperature, rainfall, and nest substrate (natural or artificial). From 2012 to 2016 we surveyed for Peregrine Falcon nests, and monitored them from February to May each year. We recorded the type of nest substrate (natural or artificial) and the nest contents (eggs, nestlings, or fledglings) at every visit. Pooled across years, we recorded 34 reproductive events that produced 42 fledglings. On average per year, there were 6.8 ± 1.6 egg-laying pairs, and 4.4 ± 1.8 were successful, with a productivity of 1.23 ± 0.06 fledglings/egg-laying pair. Monthly mean air temperatures and rainfall had no effect on breeding parameters; however, there were significant relationships with type of nest substrates. On average, we found falcons had greater nesting success and productivity on artificial substrates (83 ± 15% and 1.91 ± 0.12 fledglings/egg-laying pair) than on natural substrates (36 ± 21% and 0.36 ± 0.21 fledglings/egg-laying pair). Compared to the 1998 estimate, the number of egg-laying pairs in Guerrero Negro has more than doubled (from four to nine); this wetland area currently holds the largest number of breeding pairs along the Baja California Peninsula.